E-isomeric fullerene derivatives

ABSTRACT

An E-isomeric fulleropyrrolidine compound of formula (I):  
                 
 
     is disclosed. Also disclosed is a method for preparing and polymers prepared from such a compound.

CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application is a continuation-in-part of U.S. Ser. No.08/976,532, filed Nov. 20, 1997, which, in turn, is acontinuation-in-part of U.S. Ser. No. 8/893,055, filed Jul. 15, 1997,now U.S. Pat. No. 5,648,523, which, in turn, is a continuation-in-partof U.S. Ser. No. 08/547,714, filed Oct. 26, 1995, now U.S. Pat. No.5,648,523.

BACKGROUND OF THE INVENTION

[0002] Cancer remains a formidable disease with a high mortality rate intoday's society. Indeed, cancer is second only to cardiovascular diseaseas a cause of death, killing one out of four people in developedcountries.

[0003] Cancerous tumors commonly originate from normal cells whichtransform into malignant cells or tumors. The initial tumor growth maybe slow and thus may be difficult to detect. The growth often becomesmore aggressive and invasive with time, eventually spreading throughoutthe whole body and resulting in death.

[0004] Photodynamic therapy (PDT) is one of the methods for treatingtumors. For review, see Dougherty, T. J. Photochem. Photobiol. 1993, 58,895. At present, the most commonly used sensitizers for clinical PDTpractices are Photofrin II, an enriched active fraction ofhematoporphyrin derivatives, and disulfonated aluminum phthalocyanine.These compounds, once photoactivated, induce severe oxidative damage tothe structure of lipids, proteins, and nucleic acids. Since manybiologically active molecules, e.g., DNA, demonstrate higher affinitytoward stereospecific ligands, it is therefore desirable to developstereospecific PDT sensitizers to enhance cytotoxicity of such antitumoragents.

SUMMARY

[0005] An aspect of this invention relates to a compound of formula (I):

[0006] F_(f) is F(—K)_(m)(—Y—Z)_(q). F is a fullerene core. Each K,independently, is —OH, —SH, —NH₂, —NHOH, —SO₃H, —OSO₃H, —CO₂H, —CONH₂,—CONHNH₂, —P(OH)₃, —PO(OH)₂, —O—PO(OH)₂, —O—PO(OH)—O—PO(OH)₂,—O—PO(O⁻)—O—CH₂CH₂—NH₃ ⁺, —O—PO(O⁻)—O—CH₂CH₂—N⁺(CH₃)₃, -glycoside,—OCH₃, —OCH₂(CHOH)₄—CH₂OH, —OCH₂(CHOH)₂—CH₂OH, —NH—CH₂—CO₂H,—[CH(CO₂H)—CH₂]₁₋₁₀₀—OH, —[CH(CO₂R⁸)—CH₂]₁₋₁₀₀—OH,—[C(CH₃)(CO₂H)—CH₂]₁₋₁₀₀—OH, —[C(CH₃)(CO₂R⁸)—CH₂]₁₋₁₀₀—OH, —N(OH)₂, —NH₃⁺, —N⁺H₂R^(a), —N⁺HR^(a)R^(b), or —N⁺R^(a)R^(b)R^(c). Each Y is —A—B—,in which A is —O—, —NH—, —S—, —CO—O—, —O—CO—, O—CO—O—, —O—CO—NH—,—NH—CO—NH—, —CO—NH—, or —NH—CO—; and B is —R^(a)—O—[Si(CH₃)₂—O—]₁₋₁₀₀,C₁₋₂₀₀₀alkyl, C₆₋₄₀ aryl, C₇₋₂₀₀₀ alkylaryl, C₇₋₂₀₀₀arylalkyl, (C₁₋₃₀alkyl ether)₁₋₁₀₀, (C₆₋₄₀ aryl ether)₁₋₁₀₀, (C₇₋₂₀₀₀ alkylarylether)₁₋₁₀₀, (C₇₋₂₀₀₀ arylalkyl ether)₁₋₁₀₀, (C₁₋₃₀ alkylthioether)₁₋₁₀₀, (C₆₋₄₀ aryl thioether)₁₋₁₀₀, (C₇₋₂₀₀₀ alkylarylthioether)₁₋₁₀₀, (C₇₋₂₀₀₀ arylalkyl thioether)₁₋₁₀₀, (C₂₋₅₀ alkylester),₁₋₁₀₀, (C₇₋₂₀₀₀ aryl ester)₁₋₁₀₀, (C₈₋₂₀₀₀ alkylaryl ester)₁₋₁₀₀,(C₈₋₂₀₀₀arylalkyl ester)₁₋₁₀₀, —R⁸—CO—O—(C₁₋₃₀ alkyl ether)₁₋₁₀₀,—R^(a)—CO—O—(C₆₋₄₀ aryl ether)₁₋₁₀₀, —R^(a)—CO—O—(C₇₋₂₀₀₀ alkylarylether)₁₋₁₀₀, —R^(a)—CO—O—(C₇₋₂₀₀₀ arylalkyl ether) ₁₋₁₀₀, (C₄₋₅₀alkylurethane)₁₋₁₀₀, (C₁₄₋₆₀aryl urethane)₁₋₁₀₀, (C₁₀₋₂₀₀₀ alkylarylurethane)₁₋₁₀₀, (C₁₀₋₂₀₀₀ arylalkyl urethane)₁₋₁₀₀, (C₅₋₅₀ alkylurea)₁₋₁₀₀, (C₁₄₋₆₀ aryl urea)₁₋₁₀₀, (C₁₀₋₂₀₀₀ alkylaryl urea)₁₋₁₀₀,(C₁₀₋₂₀₀₀ arylalkyl urea)₁₋₁₀₀, (C₂₋₅₀ alkyl amide)₁₋₁₀₀, (C₇₋₆₀ arylamide)₁₋₁₀₀, (C₈₋₂₀₀₀ alkylaryl amide)₁₋₁₀₀, (C₈₋₂₀₀₀ arylalkylamide)₁₋₁₀₀, (C₃₋₃₀ alkyl anhydride)₁₋₁₀₀, (C₈₋₅₀ aryl anhydride)₁₋₁₀₀,(C₉₋₂₀₀₀ alkylaryl anhydride)₁₋₁₀₀, (C₉₋₂₀₀₀ arylalkyl anhydride)₁₋₁₀₀,(C₂₋₃₀ alkyl carbonate)₁₋₁₀₀, (C₇₋₅₀ aryl carbonate)₁₋₁₀₀, (C₈₋₂₀₀₀alkylaryl carbonate)₁₋₁₀₀, (C₈₋₂₀₀₀ arylalkyl carbonate)₁₋₁₀₀,—R^(a)—O—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₁₋₃₀alkyl ether, C₆₋₄₀aryl ether, C₇₋₂₀₀₀ alkylaryl ether, or C₇₋₂₀₀₀arylalkyl ether)₁₋₁₀₀,—R^(a)—O—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₂₋₅₀ alkyl ester, C₇₋₆₀aryl ester, C₈₋₂₀₀₀ alkylaryl ester, or C₈₋₂₀₀₀ arylalkyl ester)₁₋₁₀₀,—R^(a)—O—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₁₋₃₀ alkyl ether, C₆₋₄₀aryl ether, C₇₋₂₀₀₀ alkylaryl ether, or C₇₋₂₀₀₀ arylalkylether)₁₋₁₀₀—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—, —R^(a)—O—CO—NH—(R^(b)or Ar—R^(b)—Ar)—NH—CO—O—(C₂₋₅₀ alkyl ester, C₇₋₆₀ aryl ester, C₈₋₂₀₀₀alkylaryl ester, or C₈₋₂₀₀₀ arylalkyl ester)₁₋₁₀₀-R^(c)—O—CO—NH—(R^(b)or Ar—R^(b)—Ar)—NH—CO—O—, —R^(a)—NH—CO—NH—(R^(b) orAr—R^(b)—Ar)—NH—CO—O—(C₁₋₃₀ alkyl ether, C₆₋₄₀ aryl ether, C₇₋₂₀₀₀alkylaryl ether, or C₇₋₂₀₀₀ arylalkyl ether)₁₋₁₀₀,—R^(a)—NH—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₂₋₅₀ alkyl ester, C₇₋₆₀aryl ester, C₈₋₂₀₀₀ alkylaryl ester, or C₈₋₂₀₀₀ arylalkyl ester)₁₋₁₀₀,—R^(a)—NH—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₁₋₃₀ alkyl ether, C₆₋₄₀aryl ether, C₇₋₂₀₀₀ alkylaryl ether, or C₇₋₂₀₀₀ arylalkylether)₁₋₁₀₀—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—,—R^(a)—NH—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₂₋₅₀ alkyl ester, C₇₋₆₀aryl ester, C₈₋₂₀₀₀ alkylaryl ester, or C₈₋₂₀₀₀ arylalkylester)₁₋₁₀₀-R^(c)—O—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—,—R^(a)—O—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—NH—(C₂₋₅₀ alkyl amide, C₇₋₆₀aryl amide, C₈₋₂₀₀₀ alkylaryl amide, or C₈₋₂₀₀₀ arylalkyl amide)₁₋₁₀₀,—R^(a)—NH—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—NH—(C₂₋₅₀ alkyl amide,C₇₋₆₀ aryl amide, C₈₋₂₀₀₀ alkylaryl amide, or C₈₋₂₀₀₀ arylalkylamide)₁₋₁₀₀, or a bond; each Z, independently, is -G-D, wherein G is—R^(a)—, —R^(a)—Ar—, —Ar—R^(a)—, or —Ar—; and D is —H, —OH, —SH, —NH₂,—NHOH, —SO₃H, —OSO₃H, —CO₂H, —CONH₂, —CONHNH₂, —CH(NH₂)—CO₂H,—NH—CH₂—CO₂H, —P(OH)3, —PO(OH)₂, —O—PO(OH)₂, —O—PO(OH)—O—PO(OH)₂,—O—PO(O⁻)—O—CH₂CH₂NH₃ ⁺, —O—PO(O⁻)—O—CH₂CH₂—N⁺(CH₃)₃, -glycoside,-oligosaccharide, —CO-glycoside, —CO-oligosaccharide, —OCH₃,—OCH₂(CHOH)₄—CH₂OH, —OCH₂(CH OH)₂—CH₂OH, —CO—OCH₂(CHOH)₄—CH₂OH,—C₆H₃(OH)₂, —N(CH₂CO₂H)₂, —CO—N(CH₂CO₂H)₂, —CO—NH—C(CH₂CH₂CO₂H)₃,—CO—NH—C(CH₂CH₂OH)₃, —[CH₂—CH(CO₂R^(a))]₁₋₁₀₀—H, —NH₃ ⁺, —N⁺H₂R^(a),—N⁺HR^(a)R^(b), or —N⁺R^(a)R^(b)R^(c). Each of R^(a), R^(b), and R^(c),independently, is C₁₋₂₀ alkyl and Ar is aryl. q is 0-30, and m is 0-30.Note that the sum of q and m is 0-30. Each of R¹ and R⁴, independently,is ═O or C₁₋₂₀ hydrocarbon. A hydrocarbon is a moiety containing carbonand hydrogen, e.g., alkyl, alkenyl, or alkynyl. Each of R² and R⁵,independently, is C₁₋₂₀ hydrocarbon; wherein R¹ and R², or R⁴ and R⁵ canjoin together to form C₆₋₄₀ aryl which is optionally substituted withhalide, —OH, —NHNH₂, —NH₂OH, —NH—CH₂—CO₂H, —CH₂—CH₂-D, —CH₂—B—Z,—CO—CH₂-D, —CO—B—Z, —O—B—Z, or —NH-B-Z. Each of R³ and R⁶,independently, is —H, CH₂-D, —B—Z, -G-E, -G-CO-E, or a side chain of anamino acid. E is E₁, E₂, or E₃, in which E₁ is Y₁,Y₂-amino,(Y₁,Y₂-alkyl)-amino, Y₁,Y₂-ethylenediamino, (dihydroxymethyl)alkylamino,(X₁,X₃-aryl)amino, or X₁,X₃-aryloxy; E₂ is Y₁,Y₂-alkoxy,(Y₁,Y₂-amino)alkoxy, (Y₁,Y₂,Y₃-aryl)oxy, (dihydroxyalkyl)-aryloxy,(Y₁,Y₂,Y₃-alkyl)amino, (Y₁,Y₂,Y₃-aryl)amino, dihydroxyalkylamino,Y₁,Y₂,Y₃-alkoxy, (trihydroxyalkyl)alkoxy, (trihydroxyalkyl)alkylamino,(dicarboxyalkyl)amino, (Y₁,Y₂,Y₃-alkyl)thio, (X₁,X₃-aryl)thio,(Y₁,Y₂-alkyl)thio, (dihydroxyalkyl)thio, Y₁,Y₂-dioxoalkyl, ortri-(Y₁,Y₂,Y₃-methylaminocarboxyethyl)methylamino; and E₃ is((glycosidyl)oxoheteroaryl)amino, ((glycosidyl)oxoaryl)amino,(X₁,X₂,X₃-heteroaryl)amino, (X₁-diarylketone)amino, (X,X₁-oxoaryl)amino,(X,X₁-dioxoaryl)amino, (Y₁-alkyl,Y₂-alkyldioxoheteroaryl)amino,(Y₁-alkyl,Y₂-alkyldioxoaryl)amino,(di(Y₁,Y₂-methyl)dioxoheteroaryl)amino,(di(Y₁,Y₂-methyl)dioxoaryl)amino, ((glycosidyl)heteroaryl)amino,((glycosidyl)aryl)amino, ((carboxylacetylalkyl)oxo-heteroaryl)amino,((carboxylacetylalkyl)oxoaryl)amino,((isopropylaminohydroxy-alkoxy)aryl)amino, (X₁,X₂,X₃-alkylaryl)amino,(X₁,X₂,X₃-heteroaryl)oxy, (isopropylaminohydroxyalkyl)aryloxy,(X₁,X₂,X₃-oxoheteroaryl)oxy, (X,₁,X₂,X₃-oxoaryl)oxy,(X₁,Y₁-oxoheteroaryl)oxy, (X₁-diarylketone)oxy, (X,X₁-oxoaryl)oxy,(X₁,X₂-dioxoaryl)oxy, (Y₁,Y₂,di-aminodihydroxy)alkyl,(X₁,X₂-heteroaryl)thio, ((tricarboxylalkyl)ethylene-diamino)alkoxy,(X₁,X₂-oxoaryl)thio, (X₁,X₂-dioxoaryl)thio, (glycosidylheteroaryl)thio,(glycosidylaryl)thio, Y₁-alkyl(thiocarbonyl)thio,Y₁,Y₂,-alkyl(thiocarbonyl)thio, Y₁,Y₂,Y₃-alkyl(thiocarbonyl)thio,(Y₁,Y₂-aminothiocarbonyl)thio, (pyranosyl)thio, cysteinyl, tyrosinyl,(phenylalainyl)amino, (dicarboxyalkyl)thio, (aminoaryl)₁₋₁₀₀amino,(pyranosyl)amino, (Y₁-aminoaryl)₁₋₁₀₀amino,(amino(sulfoaryl))₁₋₁₀₀amino, peptidyl, thymidinyl, uridinyl,guanosinyl, adenosinyl, cholesteryl, or biotinylalkoxy. X is halide.Each of X₁, X₂, and X₃, independently, is —Y₁, —O—Y₁, —S—Y₁, —NH—Y₁,—CO—O—Y₁, -O—CO-Y₁, —CO—NH—Y₁, —CO—NY₁Y₂, —NH—CO—Y₁, —SO₂—Y₁, —CHY₁Y₂,or —NY₁Y₂. Each of Y₁, Y₂, and Y₃, independently, is —Z or —B—Z. Each ofx and y, independently, is 0 or 1; and s is 1-6. Note that when x is 0,R¹ is ═O; that when y is 0, R⁴ is ═O; that when x is 1, R¹ and R²jointogether to form C₆₋₄₀ aryl; and that when y is 1, R⁴ and R⁵ jointogether to form C₆₋₄₀ aryl.

[0007] Another aspect of this invention relates to a method forpreparing a compound of formula (I). The method includes reacting acompound of formula (II):

[0008] wherein M is a Cu, Mn, Fe, Co, Ni, Ru, Rh, Os, Zn, Cr, Ti, or Zrion, with a fullerene compound F_(f) of the formula F(—K)_(m)(—Y—Z)_(q)wherein the sum of q and m is 0 to form a compound of formula (III):

[0009] M is then removed from a compound of formula (III), e.g., byusing an ion exchange resin such as Dowex, to form a compound of formula(D) wherein the sum of q and m is 0. The compound of formula (I) whereinthe sum of q and m is 0 can be further treated with a nitrating orsulfating agent to form a nitrofullerene or cyclosulfated fullerene, andcontacting the nitrofullerene or cyclosulfated fullerene with anucleophilic agent to form a compound of formula (I) wherein the sum ofq and m is greater than 0, i.e., a derivatized fulleropyrrolidinecompound of this invention.

[0010] The compound of formula (II) can be prepared by reacting acompound of formula (IV):

[0011] with a metal salt MX, wherein M is a Cu, Mn, Fe, Co, Ni, Ru, Rh,Os, Zn, Cr, Ti, or Zr ion, and X is an anion such as sulfate, halide,acetate, and nitrate. As to the compound of formula (IV), it is preparedby reacting a compound of formula (V):

[0012] with a compound of formula (VI):

[0013] Yet another aspect of this invention relates to a compound offormula (VII).

[0014] F_(f) is F(—K)_(m)(—Y—Z)_(q). F is a fullerene core. Each K,independently, is —OH, —SH, —NH₂, —NHOH, —SO₃H, —OSO₃H, —CO₂H, —CONH₂,—CONHNH₂, —P(OH)₃, —PO(OH)₂, —O—PO(OH)₂, —O—PO(OH)—O—PO(OH)₂,—O—PO(O⁻)—O—CH₂CH₂—NH₃ ⁺, —O—PO(O⁻)—O—CH₂CH₂—N⁺(CH₃)₃, -glycoside,—OCH₃, —OCH₂(CHOH)₄—CH₂OH, —OCH₂(CHOH)₂—CH₂OH, —NH—CH₂—CO₂H,—[CH(CO₂H)—CH₂]₁₋₁₀₀—OH, —[CH(CO₂R^(a))—CH₂]₁₋₁₀₀—OH,—[C(CH₃)(CO₂H)—CH₂]₁₋₁₀₀—OH, —[C(CH₃)(CO₂R^(a))—CH₂]₁₋₁₀₀—OH, —N(OH)₂,—NH₃ ⁺, —N⁺H₂R^(a), —N⁺HR^(a)R^(b), or —N⁺R^(a)R^(b)R^(c). Each Y is-A-B—, in which A is —O—, —NH—, —S—, —CO—O—, —O—CO—, —O—CO—O—,—O—CO—NH—, —NH—CO—NH—, —CO—NH—, or —NH—CO—; and B is—R^(a)—O—[Si(CH₃)₂—O—]₁₋₁₀₀, C₁₋₂₀₀₀ alkyl, C₆₋₄₀ aryl, C₇₋₂₀₀₀alkylaryl, C₇₋₂₀₀₀ arylalkyl, (C₁₋₃₀ alkyl ether)₁₋₁₀₀, (C₆₋₄₀ arylether)-I100, (C₇₋₂₀₀₀ ether)₁₋₁₀₀, (C₇₋₂₀₀₀ arylalkyl ether)₁₋₁₀₀,(C₁₋₃₀ alkyl thioether)₁₋₁₀₀, (C₆₋₄₀ aryl thioether)₁₋₁₀₀, (C₇₋₂₀₀₀alkylaryl thioether)₁₋₁₀₀, (C₇₋₂₀₀₀ arylalkyl thioether)₁₋₁₀₀(C₂₋₅₀alkyl ester)₁₋₁₀₀, (C₇₋₂₀₀₀ aryl ester)₁₋₁₀₀, (C₈₋₂₀₀₀alkylarylester)₁₋₁₀₀, (C₈₋₂₀₀₀ arylalkyl ester)₁₋₁₀₀, —R^(a)—CO—O—(C₁₋₃₀alkylether)₁₋₁₀₀, —R^(a)—CO—O—(C₆₋₄₀ aryl ether)₁₋₁₀₀,—R^(a)—CO—O—(C₇₋₂₀₀₀alkylaryl ether)₁₋₁₀₀, —R^(a)—CO—O(C₇₋₂₀₀₀ arylalkylether)₁₋₁₀₀, (C₄₋₅₀ alkyl urethane)_(1-100, (C) ₁₄₋₆₀arylurethane)₁₋₁₀₀, (C₁₀₋₂₀₀₀ alkylaryl urethane)₁₋₁₀₀, (C₁₀₋₂₀₀₀ arylalkylurethane)₁₋₁₀₀, (C₅₋₅₀ alkyl urea)₁₋₁₀₀, (C₁₄₋₆₀ aryl urea)₁₋₁₀₀,(C₁₀₋₂₀₀₀ alkylaryl urea)₁₋₁₀₀, (C₁₀₋₂₀₀₀ arylalkyl urea)₁₋₁₀₀, (C₂₋₅₀alkyl amide)₁₋₁₀₀, (C₇₋₆₀ aryl amide)₁₋₁₀₀, (C₈₋₂₀₀₀ alkylarylamide)₁₋₁₀₀, (C₈₋₂₀₀₀ arylalkyl amide)₁₋₁₀₀, (C₃₋₃₀ alkylanhydride)₁₋₁₀₀, (C₈₋₅₀ aryl anhydride)₁₋₁₀₀, (C₉₋₂₀₀₀ alkylarylanhydride)₁₋₁₀₀, (C₉₋₂₀₀₀ arylalkyl anhydride)₁₋₁₀₀, (C₂₋₃₀ alkylcarbonate)₁₋₁₀₀, (C₇₋₅₀ aryl carbonate)₁₋₁₀₀, (C₈₋₂₀₀₀ alkylarylcarbonate)₁₋₁₀₀, (C₈₋₂₀₀₀ arylalkyl carbonate)₁₋₁₀₀,—R^(a)-O—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₁₋₃₀ alkyl ether, C₆₋₄₀aryl ether, C₇₋₂₀₀₀ alkylaryl ether, or C₇₋₂₀₀₀ arylalkyl ether)₁₋₁₀₀,—R^(a)—O—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₂₋₅₀ alkyl ester, C₇₋₆₀aryl ester, C₈₋₂₀₀₀ alkylaryl ester, or C₈₋₂₀₀₀ arylalkyl ester)₁₋₁₀₀,—R^(a)—O—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₁₋₃₀ alkyl ether, C₆₋₄₀aryl ether, C₇₋₂₀₀₀ alkylaryl ether, or C₇₋₂₀₀₀ arylalkylether)₁₋₁₀₀-CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—, —R^(a)—O—CO—NH—(R^(b)or Ar—R^(b)—Ar)—NH—CO—O—(C₂₋₅₀ alkyl ester, C₇₋₆₀ aryl ester, C₈₋₂₀₀₀alkylaryl ester, or C₈₋₂₀₀₀ arylalkyl ester)₁₋₁₀₀-R^(c)—O—CO—NH—(R^(b)or Ar—R^(b)—Ar)—NH—CO—O—, —R^(a)—NH—CO—NH—(R^(b) orAr—R^(b)—Ar)—NH—CO—O—(C₁₋₃₀ alkyl ether, C₆₋₄₀ aryl ether, C₇₋₂₀₀₀alkylaryl ether, or C₇₋₂₀₀₀ arylalkyl ether)₁₋₁₀₀,—R^(a)—NH—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₂₋₅₀ alkyl ester, C₇₋₆₀aryl ester, C₈₋₂₀₀₀ alkylaryl ester, or C₈₋₂₀₀₀ arylalkyl ester)₁₋₁₀₀,—R^(a)—NH—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₁₋₃₀ alkyl ether, C₆₋₄₀aryl ether, C₇₋₂₀₀₀ alkylaryl ether, or C₇₋₂₀₀₀ arylalkylether)₁₋₁₀₀—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—,—R^(a)—NH—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₂₋₅₀ alkyl ester, C₇₋₆₀aryl ester, C₈₋₂₀₀₀ alkylaryl ester, or C₈₋₂₀₀₀ arylalkylester)₁₋₁₀₀—R^(a)—O—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—,—R^(a)—O—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—NH—(C₂₋₅₀ alkyl amide, C₇₋₆₀aryl amide, C₈₋₂₀₀₀ alkylaryl amide, or C₈₋₂₀₀₀ arylalkyl amide)₁₋₁₀₀,—R^(a)—NH—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—NH—(C₂₋₅₀ alkyl amide,C₇₋₆₀ aryl amide, C₈₋₂₀₀₀ alkylaryl amide, or C₈₋₂₀₀₀ arylalkylamide)₁₋₁₀₀, or a bond; each Z, independently, is -G-D, wherein G is—R^(a)—, —R^(a)—Ar—, —Ar—R^(a)—, or —Ar—; and D is —H, —OH, —SH, —NH₂,—NHOH, —SO₃H, —OSO₃H, —CO₂H, —CONH₂, —CONHNH₂, —CH(NH₂)—CO₂H,—NH—CH₂—CO₂H, —P(OH)₃, —PO(OH)₂, —O—PO(OH)₂, —O—PO(OH)—O—PO(OH)₂,—O—PO(O⁻)—O—CH₂CH₂NH₃ ⁺, —O—PO(O⁻)—O—CH₂CH₂—N⁺(CH₃)₃, -glycoside,-oligosaccharide, —CO-glycoside, —CO-oligosaccharide, —OCH₃,—OCH₂(CHOH)₄—CH₂OH, —OCH₂(CHOH)₂—CH₂OH, —CO—OCH₂(CHOH)₄—CH₂OH,—C₆H₃(OH)₂, —N(CH₂CO₂H)₂, —CO—N(CH₂CO₂H)₂, —CO—NH—C(CH₂CH₂CO₂H)₃,—CO—NH—C(CH₂CH₂OH)₃, —[CH₂—CH(CO₂R^(a))]₁₋₁₀₀—H, —NH₃ ⁺, —N⁺H₂R^(a),—N⁺HR^(a)R^(b), or —N⁺R^(a)R^(b)R^(c). Each of R^(a), R^(b), and R^(c),independently, is C₁₋₂₀ alkyl and Ar is aryl. q is 0-30, and m is 0-30.Note that the sum of q and m is 0-30. Each of R¹ and R⁴, independently,is ═O or C₁₋₂₀ hydrocarbon. Each of R² and R⁵, independently, is C₁₋₂₀hydrocarbon. R¹ and R², or R⁴ and R⁵ can join together to form C₆₋₄₀aryl which is optionally substituted with halide, —OH, —NHNH₂, —NH₂OH,—NH—CH₂—CO₂H, —CH₂—CH₂-D, —CH₂—B—Z, —CO—CH₂-D, CO—B—Z, —O—B—Z, or—NH—B—Z. Each of R³ and R⁶, independently, is —H, —CH₂-D, —B—Z, -G-E,G-CO-E or a side chain of an amino acid. Each of B, D, and Z having beendefined above. E is E₁, E₂, or E₃, in which E₁ is Y₁,Y₂-amino,(Y₁,Y₂-alkyl)-amino, Y₁,Y₂-ethylenediamino,(dihydroxymethyl)-alkylamino, (X₁,X₃-aryl)amino, or X₁,X₃-aryloxy; E₂ isY₁,Y₂-alkoxy, (Y₁,Y₂-amino)alkoxy, (Y₁,Y₂,Y₃-aryl)oxy,(dihydroxyalkyl)-aryloxy, (Y₁,Y₂,Y₃-alkyl)amino, (Y₁,Y₂,Y₃-aryl)amino,dihydroxyalkylamino, Y₁,Y₂,Y₃-alkoxy, (trihydroxyalkyl)alkoxy,(trihydroxyalkyl)-alkylamino, (dicarboxyalkyl)amino,(Y₁,Y₂,Y₃-alkyl)thio, (X₁,X₃-aryl)thio, (Y₁,Y₂-alkyl)thio,(dihydroxyalkyl)thio, Y₁,Y₂-dioxoalkyl, ortri-(Y₁,Y₂,Y₃-methylaminocarboxyethyl)methylamino; and E₃ is((glycosidyl)oxoheteroaryl)amino, ((glycosidyl)oxoaryl)amino,(X₁,X₂,X₃-heteroaryl)amino, (X₁-diarylketone)amino, (X,X₁-oxoaryl)amino,(X,X₁-dioxoaryl)amino, (Y₁-alkyl,Y₂-alkyldioxoheteroaryl)amino,(Y₁-alkyl,Y₂-alkyldioxoaryl)amino, (di(Y₁,Y₂-methyl)dioxoheteroaryl)amino, (di(Y₁,Y₂-methyl)dioxoaryl)amino, ((glycosidyl)heteroaryl)amino,((glycosidyl)aryl)amino, ((carboxylacetylalkyl)oxo-heteroaryl)amino,((carboxylacetylalkyl)oxoaryl)amino,((isopropylaminohydroxy-alkoxy)aryl)amino, (X₁,X₂,X₃-alkylaryl)amino,(X₁,X₂,X₃-heteroaryl)oxy, (isopropylaminohydroxyalkyl)aryloxy,(X₁,X₂,X₃-oxoheteroaryl)oxy, (X₁,X₂,X₃-oxoaryl)oxy,(X₁,Y₁-oxoheteroaryl)oxy, (X₁-diarylketone)oxy, (X,X₁-oxoaryl)oxy,(X₁,X₂-dioxoaryl)oxy, (Y₁,Y₂,di-aminodihydroxy)alkyl,(X₁,X₂-heteroaryl)thio, ((tricarboxylalkyl)ethylene-diamino)alkoxy,(X₁,X₂-oxoaryl)thio, (X₁,X₂-dioxoaryl)thio, (glycosidylheteroaryl)thio,(glycosidylaryl)thio, Y₁-alkyl(thiocarbonyl)thio,Y₁,Y₂,-alkyl(thiocarbonyl)thio, Y₁,Y₂,Y₃-alkyl(thiocarbonyl)thio,(Y₁,Y₂-aminothio-carbonyl)thio, (pyranosyl)thio, cysteinyl, tyrosinyl,(phenylalainyl)amino, (dicarboxyalkyl)thio, (aminoaryl)₁₋₁₀₀amino,(pyranosyl)amino, (Y₁-aminoaryl)₁₋₁₀₀amino,(amino(sulfoaryl))₁₋₁₀₀amino, peptidyl, thymidinyl, uridinyl,guanosinyl, adenosinyl, cholesteryl, or biotinylalkoxy. X is halide.Each of X₁, X₂, and X₃, independently, is —Y₁, —O—Y₁, —S—Y₁, —NH—Y₁,—CO—O—Y₁, ₁O—CO—Y₁, —CO—NH—Y₁, —CO—NY₁Y₂, —NH—CO—Y₁, —SO₂—Y₁, —CHY₁Y₂,or —NY₁Y₂. Each of Y₁, Y₂, and Y₃, independently, is —Z or —B—Z. R⁷ is—R^(d) or —O—R^(c). R^(d) is —OH, —OM, —NHNH₂, —NHOH, —NH—CH₂—CO₂H,—O—B—Z, —NH—B—Z, -E, -O-G-E, —NH-G-E, —O-G-CO-E, or —NH-G-CO-E. M is Cu,Mn, Fe, Co, Ni, Ru, Rh, Os, Zn, Cr, Ti, or Zr ion. Re is —H, —CH₂—CH₂-D,—CH₂—B—Z, —CH₂-G-E, —CH₂-G-CO-E, —CO—CH₂-D, —CO—B—Z, —CO-G-E, or—CO-G-CO-E. R⁸ is R^(e). R⁹ is —O— or a bond. R¹⁰ is —R^(d) or —R^(e).Each of x and y, independently, is 0 or 1; and p is 1-30. Note that whenx is 0, R¹ is ═O, and R⁷ is —R^(d); that when y is 0, R⁴ is ═O, and R⁹is a bond, and R¹⁰ is —R^(d); that when x is 1, R¹ and R² join togetherto form C₆₋₄₀ aryl, and R⁷ is —O—R^(e); and that when y is 1, R⁴ and R⁵join together to form C₆₋₄₀ aryl, R⁹ is —O—, and R¹⁰ is —R^(e). Inaddition, when p is greater than 1, x is 0.

[0015] Still another aspect of this invention relates to a compound offormula (VIII):

[0016] F_(f) is F(—K)_(m)(—Y—Z)_(q). F is a fullerene core. Each K,independently, is —OH, —SH, —NH₂, —NHOH, —SO₃H, —OSO₃H, —CO₂H, —CONH₂,—CONHNH₂, —P(OH)₃, —PO(OH)₂, —O—PO(OH)₂, —O—PO(OH)—O—PO(OH)₂,—O—PO(O⁻)—O—CH₂CH₂—NH 3+, —O—PO(O—O—CH₂CH₂—N⁺(CH₃)₃, -glycoside, —OCH₃,—OCH₂(CHOH)₄—CH₂OH, —OCH₂(CHOH)₂—CH₂OH, —NH—CH₂—CO₂H,—[CH(CO₂H)—CH₂]₁₋₁₀₀—OH, —[CH(CO₂R^(a))—CH₂]₁₋₁₀₀—OH,—[C(CH₃)(CO₂H)—CH₂]₁₋₁₀₀—OH, —[C(CH₃)(CO₂R^(a))—CH₂]₁₋₁₀₀—OH, —N(OH)₂,—NH₃ ⁺, —N⁺H₂R^(a), —N⁺HR^(a)R^(b), or —N⁺R^(a)R^(b)R ; each Y is -A-B—,in which A is —O—, —NH—, —S—, —CO—O—, —O—CO—, —O—CO—O—, —O—CO—NH—,—NH—CO—NH—, —CO—NH—, or —NH—CO—. B is —R^(a)—O—[Si(CH₃)₂—O—]₁₋₁₀₀,C₁₋₂₀₀₀ alkyl, C₆₋₄₀ aryl, C₇₋₂₀₀₀ alkylaryl, C₇₋₂₀₀₀ alkylaryl, (C₁₋₃₀alkyl ether)₁₋₁₀₀, (C₆₋₄₀ aryl ether)₁₋₁₀₀, (C₇₋₂₀₀₀ alkylarylether)₁₋₁₀₀, (C₇₋₂₀₀₀ ether)₁₋₁₀₀, (C₁₋₃₀ alkyl thioether)₁₋₁₀₀, (C₆₋₄₀aryl thioether)₁₋₁₀₀, (C₇₋₂₀₀₀ alkylaryl thioether)₁₋₁₀₀, (C₇₋₂₀₀₀arylalkyl thioether)₁₋₁₀₀, (C₂₋₅₀ alkyl ester)₁₋₁₀₀, (C₇₋₂₀₀₀ arylester)₁₋₁₀₀, (C₈₋₂₀₀₀ alkylaryl ester)₁₋₁₀₀, (C₈₋₂₀₀₀ arylalkylester)₁₋₁₀₀, —R^(a)—CO—O—(C₁₋₃₀ alkyl ether)₁₋₁₀₀, —R^(a)—CO—O—(C₆₋₄₀aryl ether)₁₋₁₀₀, —R^(a)—CO—O—(C₇₋₂₀₀₀ alkylaryl ether)₁₋₁₀₀,—R^(a)—CO—O—(C₇₋₂₀₀₀ arylalkyl ether)₁₋₁₀₀, (C₄₋₅₀ alkyl urethane)₁₋₁₀₀,(C₁₄₋₆₀ aryl urethane)₁₋₁₀₀, (C10-2000 alkylaryl urethane)₁₋₁₀₀,(C₁₀₋₂₀₀₀ arylalkyl urethane)₁₋₁₀₀, (C₅₋₅₀ alkyl urea)₁₋₁₀₀, (C₁₄₋₆₀aryl urea)₁₋₁₀₀, (C₁₀₋₂₀₀₀ alkylaryl urea)₁₋₁₀₀, (C₁₀₋₂₀₀₀ arylalkylurea)₁₋₁₀₀, (C₂₋₅₀ alkyl amide)₁₋₁₀₀, (C₇₋₆₀ aryl amide)₁₋₁₀₀, (C₈₋₂₀₀₀alkylaryl amide)₁₋₁₀₀, (C₈₋₂₀₀₀ arylalkyl amide)₁₋₁₀₀, (C₃₋₃₀ alkylanhydride)₁₋₁₀₀, (C₈₋₅₀ aryl anhydride)₁₋₁₀₀, (C₉₋₂₀₀₀ alkylarylanhydride)₁₋₁₀₀, (C₉₋₂₀₀₀ arylalkyl anhydride)₁₋₁₀₀, (C₂₋₃₀ alkylcarbonate)₁₋₁₀₀, (C₇₋₅₀ aryl carbonate)₁₋₁₀₀, (C₈₋₂₀₀₀ alkylarylcarbonate)₁₋₁₀₀, (C₈₋₂₀₀₀ arylalkyl carbonate)₁₋₁₀₀,—R^(a)—O—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₁₋₃₀ alkyl ether, C₆₋₄₀aryl ether, C₇₋₂₀₀₀ alkylaryl ether, or C₇₋₂₀₀₀ arylalkyl ether)₁₋₁₀₀,—R^(a)—O—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₂₋₅₀ alkyl ester, C₇₋₆₀aryl ester, C₈₋₂₀₀₀ alkylaryl ester, or C₈₋₂₀₀₀ arylalkyl ester)₁₋₁₀₀,—R^(a)—O—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C¹⁻³⁰ alkyl ether, C₆₋₄₀aryl ether, C₇₋₂₀₀₀ alkylaryl ether, or C₇₋₂₀₀₀ arylalkylether)₁₋₁₀₀-CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—, —R^(a)—O—CO—NH—(R^(b)or Ar—R^(b)—Ar)—NH—CO—O—(C₂₋₅₀ alkyl ester, C₇₋₆₀ aryl ester, C₈₋₂₀₀₀alkylaryl ester, or C₈₋₂₀₀₀ arylalkyl ester)₁₋₁₀₀-R^(c)—O—CO—NH—(R^(b)or Ar—R^(b)—Ar)—NH—CO—O—, —R^(a)—NH—CO—NH—(R^(b) orAr—R^(b)—Ar)—NH—CO—O—(C₁₋₃₀ alkyl ether, C₆₋₄₀ aryl ether, C₇₋₂₀₀₀alkylaryl ether, or C₇₋₂₀₀₀ arylalkyl ether)₁₋₁₀₀,—R^(a)—NH—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₂₋₅₀ alkyl ester, C₇₋₆₀aryl ester, C₈₋₂₀₀₀ alkylaryl ester, or C₈₋₂₀₀₀ arylalkyl ester)₁₋₁₀₀,−R^(a)—NH—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₁₋₃₀ alkyl ether, C₆₋₄₀aryl ether, C₇₋₂₀₀₀ alkylaryl ether, or C₇₋₂₀₀₀ arylalkylether)₁₋₁₀₀—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—,—R^(a)—NH—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₂₋₅₀ alkyl ester, C₇₋₆₀aryl ester, C₈₋₂₀₀₀ alkylaryl ester, or C₈₋₂₀₀₀ arylalkylester)₁₋₁₀₀-R^(c)—O—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—,—R^(a)—O—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—NH—(C₂₋₅₀ alkyl amide, C₇₋₆₀aryl amide, C₈₋₂₀₀₀ alkylaryl amide, or C₈₋₂₀₀₀ arylalkyl amide)₁₋₁₀₀,—R^(a)—NH—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—NH—(C₂₋₅₀ alkyl amide,C₇₋₆₀ aryl amide, C₈₋₂₀₀₀ alkylaryl amide, or C₈₋₂₀₀₀ arylalkylamide)₁₋₁₀₀, or a bond. Each Z, independently, is -G-D, wherein G is—R^(a)—, —R^(a)—Ar—, —Ar—R^(a)—, or —Ar—; and D is —H, —OH, —SH, —NH₂,—NHOH, —SO₃H, —OSO₃H, —CO₂H, —CONH₂, —CONHNH₂, —CH(NH₂)—CO₂H,—NH—CH₂—CO₂H, —P(OH)₃, —PO(OH)₂, —O—PO(OH)₂, —O—PO(OH)—O—PO(OH)₂,—O—PO(O⁻)—O—CH₂CH₂NH₃ ⁺, —O—PO(O⁻)—O—CH₂CH₂—N⁺(CH₃)₃, -glycoside,-oligosaccharide, —CO-glycoside, —CO-oligosaccharide, —OCH₃,—OCH₂(CHOH)₄—CH₂OH, —OCH₂(CHOH)₂—CH₂OH, —CO—OCH₂(CHOH)₄—CH₂OH,—C₆H₃(OH)₂, —N(CH₂CO₂H)₂, —CO—N(CH₂, —CO—NH—C(CH₂CH₂CO₂H)3,—CO—NH—C(CH₂CH₂OH)₃, —[CH₂—CH(CO₂R^(a))]₁₋₁₀₀—H, —NH₃ ⁺, —N⁺H₂R^(a),—N⁺HR^(a)R^(b), or —N⁺R^(a)R^(b)R^(c). Each of R^(a), R^(b), and R^(c),independently, is C₁₋₂₀ alkyl and Ar is aryl. q is 0-30, and m is 0-30.Note that the sum of q and m is 0-30. Each of R¹ and R⁴, independently,is ═O or C₁₋₂₀ hydrocarbon; and each of R² and R⁵, independently, isC₁₋₂₀ hydrocarbon. R¹ and R², or R⁴ and R⁵ can join together to formC₆₋₄₀ aryl which is optionally substituted with halide, —OH, —NHNH₂,—NH₂OH, —NH—CH₂—CO₂H, —CH₂—CH₂-D, —CH₂—B—Z, —CO—CH₂-D, CO—B—Z, —O—B—Z,or —NH—B—Z. Each of R³ and R6, independently, is —H, —CH₂-D, —B—Z, -G-E,-G-CO-E or a side chain of an amino acid. E is E₁, E₂, or E₃, in whichE₁ is Y₁,Y₂-amino, (Y₁,Y₂-alkyl)-amino, Y₁,Y₂-ethylenediamino,(dihydroxymethyl)alkylamino, (X₁,X₃-aryl)amino, or X₁,X₃-aryloxy; E₂ isY₁,Y₂-alkoxy, (Y₁,Y₂-amino)alkoxy, (Y₁,Y₂,Y₃-aryl)oxy,(dihydroxyalkyl)-aryloxy, (Y₁,Y₂,Y₃-alkyl)amino, (Y₁,Y₂,Y₃-aryl)amino,dihydroxyalkylamino, Y₁,Y₂,Y₃-alkoxy, (trihydroxyalkyl)alkoxy,(trihydroxyalkyl)alkylamino, (dicarboxyalkyl)amino,(Y₁,Y₂,Y₃-alkyl)thio, (X₁,X₃-aryl)thio, (Y₁,Y₂-alkyl)thio,(dihydroxyalkyl)thio, Y₁,Y₂-dioxoalkyl, ortri-(Y₁,Y₂,Y₃-methylaminocarboxyethyl)methylamino; and E₃ is((glycosidyl)oxoheteroaryl)amino, ((glycosidyl)oxoaryl)amino,(X₁,X₂,X₃-heteroaryl)amino, (X₁-diarylketone)amino, (X,X₁-oxoaryl)amino,(X,X₁-dioxoaryl)amino, (Y₁-alkyl,Y₂-alkyldioxoheteroaryl)amino,(Y₁-alkyl,Y₂-alkyldioxoaryl)amino,(di(Y₁,Y₂-methyl)dioxoheteroaryl)amino,(di(Y₁,Y₂-methyl)dioxoaryl)amino, ((glycosidyl)heteroaryl)amino,((glycosidyl)aryl)amino, ((carboxylacetylalkyl)oxo-heteroaryl)amino,((carboxylacetylalkyl)oxoaryl)amino,((isopropylaminohydroxy-alkoxy)aryl)amino, (X₁,X₂,X₃-alkylaryl)amino,(X₁,X₂,X₃-heteroaryl)oxy, (isopropylaminohydroxyalkyl)aryloxy,(X₁,X₂,X₃-oxoheteroaryl)oxy, (X₁,X₂,X₃-oxoaryl)oxy,(X₁,Y₁-oxoheteroaryl)oxy, (X₁-diarylketone)oxy, (X,X₁-oxoaryl)oxy,(X₁,X₂-dioxoaryl)oxy, (Y₁,Y₂,di-aminodihydroxy)alkyl,(X₁,X₂-heteroaryl)thio, ((tricarboxylalkyl)ethylene-diamino)alkoxy,(X₁,X₂-oxoaryl)thio, (X₁,X₂-dioxoaryl)thio, (glycosidylheteroaryl)thio,(glycosidylaryl)thio, Y₁-alkyl(thiocarbonyl)thio,Y₁,Y₂,-alkyl(thiocarbonyl)thio, Y₁,Y₂,Y₃-alkyl(thiocarbonyl)thio,(Y₁,Y₂-aminothiocarbonyl)thio, (pyranosyl)thio, cysteinyl, tyrosinyl,(phenylalainyl)amino, (dicarboxyalkyl)thio, (aminoaryl)₁₋₁₀₀amino,(pyranosyl)amino, (Y₁-aminoaryl)₁₋₁₀₀amino,(amino(sulfoaryl))₁₋₁₀₀amino, peptidyl, thymidinyl, uridinyl,guanosinyl, adenosinyl, cholesteryl, or biotinylalkoxy. X is halide.Each of X₁, X₂, and X₃, independently, is —Y₁, —O—Y₁, —S—Y₁, —NH—Y₁,—CO—O—Y₁, —O—CO—Y₁, —CO—NH—Y₁, —CO—NY₁Y₂, —NH—CO—Y₁, —SO₂—Y₁, —CHY₁Y₂,or —NY₁Y₂. Each of Y₁, Y₂, and Y₃, independently, is —Z or —B—Z. R⁷ is—R^(d) or —O—R^(e). R^(d) is —H, —OM, —NHNH₂, —NH OH, —NH—CH₂—CO₂H,—O—B—Z, —NH—B—Z, -E, —O—G-E, —NH-G-E, —O-G-CO-E, or —NH-G-CO-E. M is Cu,Mn, Fe, Co, Ni, Ru, Rh, Os, Zn, Cr, Ti, or Zr ion. Re is —H, —CH₂—CH₂-D,—CH₂—B—Z, —CH₂-G-E, —CH₂-G-CO-E, —CO—CH₂-D, —CO—B—Z, —CO-G-E, or—CO-G-CO-E. R⁸ is R^(e). R⁹ is —O—R^(f)— or —R^(g)—. R^(f) is—CO—B-G-O—, —CO—B-G-NH—, —CO—B-G-CO—O—, or —CO—B-G-CO—NH—. R^(g) is—NH—, —O—, —O—B-G-O—, —NH—B-G-O—, —NH—B-G-NH—, —O—CO—B-G-CO—O—, or—NH—CO—B-G-CO—NH—. R¹⁰ is —H. Each of x and y, independently, is 0 or 1;and r is 1-100. Note that when x is 0, R¹ is ═O, and R⁷ is —R^(d); thatwhen y is 0, R⁴ is ═O, and R⁹ is —R^(g), and R¹⁰ is —H; that when x is1, R¹ and R² join together to form C₆₋₄₀ aryl, and R⁷ is —O—R^(e); andthat when y is 1, R⁴ and R⁵ join together to form C₆₋₄₀ aryl, R⁹ is—O—R^(f), and R¹⁰ is —H. Further, when r is greater than 1, x is 0.

[0017] A salt of a compound of the present invention is also within thescope of this invention. For example, a salt can form between an aminomoiety and an anion such as sulfate, pyrosulfate bisulfate, sulfite,bisulfite, phosphate, monohydrogenphosphate, dihydrogenphosphate,metaphosphate, pyrophosphate, chloride, bromide, iodide, acetate,propionate, decanoate, caprylate, acrylate, formate, isobutyrate,caprate, heptanoate, propiolate, oxalate, malonate, succinate, suberate,sebacate, fumarate, or maleate.

[0018] As used herein, a fullerene core is C₆₀, C₆₁, C₆₂, C₆₃, C₆₄, C₆₅,C₇₀, C₇₆, C₇₈, C₈₂, C₈₄, or C₉₂, or La@C_(n), Ho@C_(n), Gd@C_(n), orEr@C_(n), in which n is 60, 74, or 82.

[0019] An amino acid is a molecule containing both an amino group and acarboxylic acid, e.g., alanine, aspartic acid, cysteine, glutamic acid,phenylalanine, halophenylalanine, hydroxyphenylalanine, glycine,histidine, isoleucine, lysine, leucine, methionine, asparagine,glytamine, arginine, serine, theronine, valine, tryptophan, tyrosine,2-aminobutyric acid, halophenylalanine, cyclohexylalanine, citrulline,homocitrulline, homoserine, norleucine, norvaline, or ornithine. Sidechain of an amino acid is the substituent that is bonded to the carbonatom adjacent to the carbonyl carbon, i.e., the -carbon atom. Forexample, the side chain of each of alanine and ornithine is —CH₃ and—CH₂)₃NH₂, respectively. A peptidyl is a peptide moiety containing 2-100amino acid residues.

[0020] By the term “alkyl” is meant a straight chain that contains 1-30carbon atoms, or a branched hydrocarbon chain of 3-30 carbon atoms, orcyclic hydrocarbon groups containing 3-30 carbon atoms, or otherwiseindicated. These alkyl-groups may also contain one or more double bondor triple bond and the cyclic alkyl groups may contain one or moreheteroatoms, which are, typically, nitrogen, oxygen, or sulfur. Examplesof alkyl groups include, but are not limited to, methyl, ethyl, propyl,isopropyl, butyl, isobutyl, tert-butyl, amyl, pentyl, hexyl, heptyl,octyl, nonyl, decyl, pentadecyl, icosyl, allyl, 2-butenyl, ₂-pentenyl,3-hexenyl, 4-decenyl, 5-nonadecenyl, 2-butnyl, 3-octnyl, 5-octadecnyl,cyclopropyl, cyclopentyl, cyclohexyl, cycloheptyl, adamantyl, norbornyl,isobornyl, cyclopentyl-methyl, cyclohexylmethyl, 1- or₂-cyclohexylethyl, cyclo-pentenyl, cyclohexenyl, cycloheptenyl,cyclo-octenyl, tetra-hydrofuranyl, tetrahydropyranyl, piperidinyl,morpholino and pyrrolindinyl groups.

[0021] As used herein, the term “aryl” refers to C₆₋₄₀ aromatic rings.These moieties may also be fused rings and can be fused with aryl orheteroaryl which is as defined below. Fused rings are rings that share acommon carbon-carbon bond. Typically aryl groups include phenyl,naphthyl, biphenyl, indazolyl, phenanthryl, and anthracyl.

[0022] By the term “heteroaryl” in this disclosure is meant C₆₋₄₀aromatic rings that contain one or more heteroatoms as defined above.These moieties may also be fused rings. Examples of heteroaryl groupsinclude pyridyl, pyrazinyl, pyrimidyl, furyl, pyrrolyl, thienyl,thiazolyl, oxazolyl, imidazolyl, coumarinyl, indolyl, benzofuranyl,benzthiazolyl, benzothienyl, and benzothiadiazolyl.

[0023] As used herein, the term “halide” is defined as fluoro, chloro,bromo, or iodo. The term “nucleophilic agent” is defined as anelectron-rich species that donates electrons in a reaction. Examples ofnucleophilic agents that can be employed in the preparation ofderivatized fulleropyrrolidines include amine, phenol, alkoxide,organothiolate, carbanion, organoamide anion, thiol, amino acid, andthiol carbamate anion. Note that the just-mentioned nucleophilic agentscan be unsubstituted or substituted with other functional groups.Examples of substituted nucleophilic agents include1,4-naphthoquinonyl-amine, tyrosine, dihydroxypropylthiol, and the like.

[0024] The structures of many of the moieties mentioned above are shownbelow within the pair of parentheses following each of the moieties:alkyl ether (—R—O—), aryl ether (—Ar—O—), alkylaryl ether (—R—Ar—O—),arylalkyl ether (—Ar—R—O—), alkyl thioether (—R—S—), aryl thioether(—Ar—S—), alkylaryl thioether (—R—Ar—S—), arylalkyl thioether(—Ar—R—S—), alkyl ester (—R—O—CO—, —R—CO—O—, —R₁—CO—O—R₂—O—CO—, or—R₁—O—CO—R₂—CO—O—), aryl ester (—Ar—O—CO—, —Ar—CO—O,—Ar₁—CO—O—Ar₂—O—CO—, or —Ar₁—O—CO—Ar₂—CO—O—), alkylaryl ester(—R—Ar—O—CO— or —R—Ar—CO—O—), arylalkyl ester (—Ar—R—O—CO— or—Ar—R—CO—O—), alkyl urethane (—R₁—O—CO—NH—R₂—NH—CO—O—), aryl urethane(—Ar₁—O—CO—NH—Ar₂—NH—CO—O—), alkylaryl urethane(—R₁—Ar—O—CO—NH—R₂—NH—CO—O—, —R—Ar₁—O—CO—NH—Ar₂—NH—CO—O—, or—R₁—O—CO—NH—Ar—R₂—Ar—NH—CO—O—), arylalkyl urethane(—Ar—R₁—O—CO—NH—R₂—NH—CO—O—, —Ar₁—R—O—CO—NH—Ar₂—NH—CO—O—, or—Ar₁—O—CO—NH—Ar₂—R—Ar₂—NH—CO—O—), alkyl urea(—R₁—NH—CO—NH—R₂—NH—CO—NH—), aryl urea (—Ar₁—NH—CO—NH—Ar₂—NH—CO—NH—),alkylaryl urea (—R₁-Ar—NH—CO—NH—R₂—NH—CO—NH—,—R—Ar₁—NH—CO—NH—Ar₂—NH—CO—NH—, or —R₁—NH—CO—NH—Ar—R₂—Ar—NH—CO—NH—),arylalkyl urea (—Ar—R₁—NH—CO—NH—R₂—NH—CO—NH—,—Ar₁—R—NH—CO—NH—Ar₂—NH—CO—NH—, or —Ar₁—NH—CO—NH—Ar₂—R—Ar₂—NH—CO—NH—),alkyl amide (—R—NH—CO—, —R—CO—NH—, —R_(—CO—NH—R) ₂—NH—CO—, or—R₁—NH—CO—R₂—CO—NH—), aryl amide (—Ar—NH—CO—, —Ar—CO—NH—,—Ar₁—CO—NH—Ar₂—NH—CO—, or —Ar₁—NH—CO—Ar₂—CO—NH—), alkylaryl amide(—R-Ar—NH—CO—, —R—CO—NH—Ar—NH—CO—, or —R—NH—CO—Ar—CO—NH—), arylalkylamide (—Ar—R—NH—CO—, —Ar—CO—NH—R—NH—CO—, or —Ar—NH—CO—R—CO—NH—), alkylanhydride (—R—CO—O—CO—), aryl anhydride (—Ar—CO—O—CO—), alkylarylanhydride (—R—Ar—CO—O—CO— or —R—CO—O—CO—Ar—CO—O—CO—), arylalkylanhydride (—Ar—R—CO—O—CO— or —Ar—CO—O—CO—R—CO—O—CO—), alkyl carbonate(—R—O—CO—O—), aryl carbonate (—Ar—O—CO—O—), alkylaryl carbonate(—R—Ar—O—CO—O— or —R—O—CO—O—Ar—O—CO—O—), and arylalkyl carbonate(—Ar—R—O—CO—O— or —Ar—O—CO—O—R—O—CO—O—). Note that the di-substitutionpattern on Ar can be para, meta, or ortho.

[0025] As will be discussed below, one can employ stereospecificcompounds of this invention to treat patients suffering from cancer viaphotodynamic therapy. The stereospecific nature of these compounds allowspecific interactions with many biologically active compounds, e.g.,protein receptors. The compounds of this invention can also be used todevelop chromatographic materials for purifying chiral molecules.

[0026] Other features and advantages of the present invention will beapparent from the following description of the preferred embodiments,and also from the appending claims.

DETAILED DESCRIPTION

[0027] The invention relates to sterospecific fullerene compounds, i.e.,E-isomeric fulleropyrrolidine compounds, as well as polymers made ofsuch E-isomeric compounds. Also disclosed are methods for preparingthese E-isomeric compounds and E-isomeric fulleropyrrolidine polymers.

[0028] Methods of this invention allow an E-isomeric fulleropyrrolidinecompound to be prepared directly, thereby obviating the need topurifying a racemic mixture of both E- and Z-isomers. Separation ofoptical isomers is generally very difficult due to the close physicalproperties of optical isomers. Specifically, the methods describedherein utilize a key starting material, i.e., a bicyclicimine-containing organometallic compound such asN-pyruvylidenealaninatoaquocopper (II). This bicyclic imine-containingcompound, which is formed of two difunctional compounds, effects astereospecific cycloaddition reaction when reacts with a fillerene core,e.g., C₆₀, C₇₆, or Gd@C₈₂, thus forming only one fullerene isomer, i.e.,the E-isomer.

[0029] Scheme I below illustrates a method for preparing an E-isomericfulleropyrrolidine compound of this invention wherein its two carboxylicacid moieties are substituted at the same side of the pyrrolidinemoiety. In the first step, an amino acid (H₂N—CH(R_(b))—COOH) and apyruvic acid derivative (R_(b)—C(═O)—COOH) are used as exemplarydifunctional compounds which react with each other to form a bicyclicimine-containing copper (II) complex in the presence of copper (II)acetate. See step (i). Note that the coordination of the two carboxylicacid moieties with the copper (II) ion restricts rotations of the N—Cbond with respect to the N═C bond, thus forcing the two carboxylic acidto be at the same side of the pyrrolidine that is formed between theimine moiety, i.e., —C═NC—, of the copper complex and a double bond of afullerene core, e.g., C₆₀, via a cycloaddition reaction. See step (ii).Not only does the copper (II) ion enables only one stereospecificisomer, i.e., the E-isomer, to be formed, it also prevents thermaldecarboxylation after dicarboxylic acid substituted fulleropyrrolidinesare formed. By exchanging the copper (II) ion with the proton on a Dowexresin (H⁺ form), the corresponding E-isomeric dicarboxylic acidsubstituted fulleropyrrolidine product was isolated in a high yield(>85%). See Example 1 below.

[0030] Scheme II below illustrates a method for preparing an E-isomericfulleropyrrolidine compound of this invention wherein it is substitutedwith a carboxylic acid and an aromatic ring at the same side of thepyrrolidine moiety. The only difference between the methods shown inScheme I and Scheme II lies in that the former method employs adifunctional carboxylic acid, e.g., 2-ketoglutaric acid, whereas thelatter method employs a difunctional phenol, e.g., salicylaldehyde. Thedifunctional phenol, e.g., a carbonyl-containing phenol, can then reactwith a difunctional carboxylic acid, e.g., an amino acid, in thepresence of a metal salt, e.g., Cu(OAc)₂ or CoCl₂, to form a bicyclicimine-containing metal complex. See step (i). The next two steps of themethod, i.e., cycloaddition (step (ii)) and removal of metal ions (step(iii)), are identical to those described above. See Example 7 below.

[0031] Alternatively, the bicyclic imine-containing organometalliccompound can also be formed between an amine-containing phenol, e.g.,2′-aminoacetophenone, and a carbonyl-containing carboxylic acid, e.g.,pyruvic acid, or a carbonyl-containing phenol, e.g., salicylaldehyde.

[0032] The resulting E-isomeric fulleropyrrolidine compound of formula(I) can be further derivatized, e.g., by attaching thereto amethylglucoside, by various known methods. See, e.g., U.S. Pat. No.6,020,523. For example, the fulleropyrrolidine compound can be treatedwith a nitrating agent or a sulfating agent to form anitrofulleropyrrolidine or a cyclosulfated-fulleropyrrolidineintermediate, which can then be converted into a derivatized E-isomericfulleropyrrolidine by reacting with a nucleophilic agent. Examples of anitrating agent include sodium nitrite and concentrated HNO₃, dinitrogentetraoxide, nitrogen dioxide, and fuming nitric acid. Cyclosulfatedfullerene intermediates, on the other hand, can be formed by treatingthe fullerene with neat fuming sulfuric acid in the presence of anoxidant (e.g., P₂O₅, V₂O₅, or SeO₂). Examples of a nucleophilic agentinclude primary and secondary organoamino compound, alkoxide,organothiolate, organophenol compound, carbanion, organoamide anion,thiocarbamate ion, and the like.

[0033] The E-isomeric fulleropyrrolidine compound of formula (I) canfurther react with each other to form a polymer (or an oligomer). Thepolymer formed can be a homopolymer or a copolymer, e.g., a random, ablock, or a branched copolymer. Since a compound of formula (I) containsthree termini, i.e., a pyrrolidine nitrogen ring atom and two carboxylicacid moieties (or a carboxylic moiety and a phenol hydroxy group, or twophenol hydroxyl groups), a number of polymers can be prepared viadifferent linkages. Take a fulleropyrrolidine compound containing twocarboxylic acid moieties as an example, a polymer can be formed bylinking the N-terminus (i.e., the pyrrolidine nitrogen ring atom) of afirst compound of formula (I) to the C-terminus (i.e., one of the twocarboxylic acid moieties) of a second compound of formula (I), and theN-terminus of this second compound of formula (I) can in turn be linkedto the C-terminus of a third compound of formula (I), and so on. Thispolymer design is similar to that of a peptide. The just-describedpolymer, i.e., a polymer of formula (VII), supra, can be prepared byforming an internal anhydride between the two carboxylic acid moieties,which is then treated with a base such as1,8-diazabicyclo-[5.4.0]undec-7-ene (DBU) to effect the polymerizationreaction. Due to the highly reactive nature of the anhydride moiety,derivatization of the fullerene should be done after the polymerizationstep. See Scheme III and Example 11 below.

[0034] A polymer of formula (VII) can also be prepared using afulleropyrrolidine compound having a phenol and a carboxylic acidmoiety. Since this compound (or monomer) contains one carboxylic acidand one amino group, polymerization can be effected by using commonpeptide coupling reagents, e.g., dicyclohexylcarbodiimide (DCC),benzotriazol-1-yloxytris(dimethylamino)-phosphonium hexafluorophosphate(BOP), or O-benzo-triazol-1-yl-N,N,N′,N′-tetramethyluroniumhexafluorophosphate (HBTU). Note that the hydroxy group of the phenolmoiety may need to be protected, e.g., by silyl ethers, duringpolymerization.

[0035] Alternatively, a polymer of an E-isomeric fulleropyrrolidinecompound of formula (I) can also be formed by linking the carboxylicacid moiety (or the hydroxy group of the phenol moiety) of onefulleropyrrolidine monomer to the carboxylic acid moiety of anotherfulleropyrrolidine monomer via a divalent linker, thus resulting in apolymer of formula (VIII). For example, a polyamide and a polyester canbe formed by reacting a fulleropyrrolidine compound with two carboxylicacid moieties with a diamine (e.g., ethylenediamine) and a diol (e.g.,1,3-propanediol), respectively.

[0036] An E-isomeric fulleropyrrolidine compound of formula (I) can beused in photodynamic therapy (PDT) to treat patients suffering fromcancer. See Example 16 below. The photo-induced cytotoxicity of afullerene compound is connected with its ability to cleave DNA.Specifically, photogenerated triplet fullerene intermediate is involvedin the energy transfer process which converts the ground-state tripletoxygen molecules into the excited molecular singlet oxygen ¹O₂. Singletoxygen is capable of inducing DNA damage and degeneration of othertissues that lead to mutagenic effects on biological cells. Thestereospecific-nature of an E-isomeric fulleropyrrolidine compound offormula (I) can enhance its affinity to DNA which is in the form of adouble helix. Polymers of formulas (VII) and (VIII), which contain aplurality of fulleropyrrolidine compounds of formula (I), can furtherenhance its biological activities by allowing delivery of multiplefulleropyrrolidine compounds in a single molecule.

[0037] A pharmaceutical composition containing an effective amount of afulleropyrrolidine compound of formula (I) (or a polymer formedtherefrom) is also within the scope of this invention. The use of such afulleropyrrolidine compound for the manufacture of a medicament fortreating tumors is also within the scope of this invention. Stillanother aspect of this invention is a method for treating tumor byadministering to a patient a pharmaceutical composition containing aneffective amount of a fulleropyrrolidine compound of this invention. Aneffective amount is defined as the amount which is required to confer atherapeutic effect on the treated patient, and is typically determinedbased on age, surface area, weight, and condition of the patient. Theinterrelationship of dosages for animals and humans (based on milligramsper meter squared of body surface) is described by Freireich et al.,Cancer Chemother. Rep. 1966, 50, 219. Body surface area maybeapproximately determined from height and weight of the patient. See,e.g., Scientific Tables, Geigy Pharmaceuticals, Ardley, N.Y., 1970, 537.An effective amount of a pyridyl cyanoguanidine compound of thisinvention can range from about 1 mg/kg to about 150 mg/kg (e.g., about 1mg/kg to about 100 mg/kg) . Effective doses will also vary, asrecognized by those skilled in the art, dependant on route ofadministration, excipient usage, and the possibility of co-usage withother therapeutic treatments including use of other antitumor agents andradiation therapy.

[0038] The pharmaceutical composition may be administered via theparenteral route, including orally, topically, subcutaneously,intraperitoneally, intramuscularly, and intravenously. Examples ofparenteral dosage forms include aqueous solutions of the active agent,in a isotonic saline, 5% glucose or other well-known pharmaceuticallyacceptable excipient. Solubilizing agents such as cyclodextrins, orother solubilizing agents well-known to those familiar with the art, canbe utilized as pharmaceutical excipients for delivery of the therapeuticcompounds.

[0039] A fulleropyrrolidine compound of this invention can be formulatedinto dosage forms for other routes of administration utilizingconventional methods. For example, it can be formulated in a capsule, agel seal, or a tablet for oral administration. Capsules may contain anystandard pharmaceutically acceptable materials such as gelatin orcellulose. Tablets may be formulated in accordance with conventionalprocedures by compressing mixtures of a pyridyl cyanoguanidine compoundwith a solid carrier and a lubricant. Examples of solid carriers includestarch and sugar bentonite. The fulleropyrrolidine compound can also beadministered in a form of a hard shell tablet or a capsule containing abinder, e.g., lactose or mannitol, a conventional filler, and atableting agent.

[0040] Without further elaboration, it is believed that one skilled inthe art can, based on the description herein, utilize the presentinvention to its fullest extent. The following specific examples are,therefore, to be construed as merely illustrative, and not limitative ofthe remainder of the disclosure in any way whatsoever. All publicationsrecited herein, including patents, are hereby incorporated by referencein their entirety.

EXAMPLE 1 Synthesis of E-isomer of1,3-dimethyl-fulleropyrrolidine-1,3-dicarboxylic acid

[0041] In a conical flask charged with DL-alanine (2.25 g, 25 mmol) anda mixture of water and ethanol (20 ml, 2:1) and stirred for a period of20 min was added pyruvic acid (2.2 g, 25 mmol). The reaction mixture wasstirred at ambient temperature for 1.0 h. The resulting yellowishsolution was then added copper (II) acetate (4.99 g, 25 mmol) inwater-ethanol (20 ml) and stirred for an additional 2 4 h, causingprecipitation of pale blue solids. The solids were filtered, washed withethanol, and dried to yield N-pyruvylidenealaninatoaquocopper (II)complex.

[0042] To a solution of C₆₀ (350 mg, 0.49 mmol) in o-dichlorobenzene(140 ml), N-pyruvylidenealaninatoaquocopper (II) complex (0.34 g, 1.96mmol, 4.0 equiv.) in pyridine (25 ml) was added via syringe under N₂.The solution mixture was stirred for a period of 15 h at ambienttemperature. It was added hexane (100 ml) to effect precipitation ofsolid products. The solid precipitates were isolated by centrifuge,washed with hexane (50 ml), and dried in vaccuo. It was further washedtwice by water, brine, and CH₃CN (20 ml each) and dried in vaccuo toafford brown solids of1,3-dimethyl-fulleropyrrolidine-1,3-dicarboxylatoaquocopper (II) complex(0.53 g). IR_(max) (KBr) 3424 (br, s), 1749 (w), 1716 (w), 1622 (s),1385 (s), 1218 (w), 1182 (w), 1154 (w),1070 (w), 751, 696, and 525.

[0043] Brown solids of1,3-dimethyl-fulleropyrrolidine-1,3-dicarboxylatoaquocopper (II) complex(0.5 g) were dissolved in a mixture of pyridine (25 ml) and water (25ml). It was stirred in the presence of Dowex acid resin (50WX8, 2.0 g)for a period of 2.0 h. The solid resin was filtered off. The remainingsolution was stirred further with fresh Dowex acid resin (50WX8, 1.5 g)for an additional 30 min. At the end of the ion exchanging reaction,Dowex resin was filtered. After solvent evaporation of the filtrate, theresulting dark solids were washed with ethanol and dried in vaccuo togive the product of 1,3-dimethyl-fulleropyrrolidine-1,3-dicarboxylicacid (0.4 g). IR max (KBr) 3422 (br, s), 3101 (w), 1779 (w), 1717, 1635(s), 1488, 1388, 1242, 1162, 1036, 751, 681, and 526. Treatment of1,3-dimethyl-fulleropyrrolidine-1,3-dicarboxylic acid with dil. HCl (2.0N) gave the corresponding N-protonated1,3-dimethyl-fulleropyrrolidine-1,3-dicarboxylic acid containing freecarboxylic acids. IR_(max) (KBr) 3421 (br, s), 3245, 2930, 2859, 2575(CO₂H), 1723 (s, CO₂H), 1641, 1453, 1414, 1169, 1111 (s),955 (w), 801,665 (w),599 (w), and 470.

EXAMPLE 2 Synthesis of E-isomer of1-dimethyl-3-hydroxyphenylmethyl-fulleropyrrolidine-1,3-dicarboxylicacid

[0044] In a conical flask charged with DL-tyrosine (4.52 g, 25 mmol) anda mixture of water and ethanol (20 ml, 2:1) and stirred for a period of20 min was added pyruvic acid (2.2 g, 25 mmol). The reaction mixture wasstirred at 50° C. for 2.0 h under basic condition at pH 8 10 using NaOHas a titration agent. The resulting yellowish solution was then addedcopper (II) chloride (3.4 g, 25 mmol) in water-ethanol (20 ml) andstirred for an additional 2 4 h, causing precipitation of pale bluesolids. The solids were filtered, washed with water, ethanol,diethylether, and dried to yield N-pyruvylidenetyrosinatoaquocopper (II)complex. IR max (KBr) 3490, 3371, 3290, 3151, 3052, 2971, 2932, 1613(s), 1580, 1520, 1448, 1408, 1335, 1242, 1123, 1070, 891, 848, 810, 744,705, 600, and 539.

[0045] Alternatively, in a conical flask charged with DL-alanine (2.27g, 25 mmol) and a mixture of water and ethanol (20 ml, 2:1) and stirredfor a period of 20 min was added p-hydroxyphenylpyruvic acid (4.5 g, 25mmol). The reaction mixture was stirred at ambient temperature for 2.0h. The resulting yellowish solution was then added copper (II) acetate(5.0 g, 25 mmol) in water-ethanol (20 ml) and stirred for an additional2 4 h, causing precipitation of greenish blue solids. The solids werefiltered, washed with ethanol, diethylether, and dried to yield bluesolids of N-hydroxyphenylpyruvylidene-alaninatoaquocopper (II) complex.IR_(max) (KBr) 3423, 3255, 2975, 2941, 1621 (s), 1518, 1457, 1396, 1363,1250, 1154, 1122, 859, 848, 792, 778, 715, 678, and 576.

[0046] To a solution of C₆₀ (500 mg, 0.69 mmol) in o-dichlorobenzene(150 ml), N-pyruvylidenetyrosinatoaquocopper (II) complex (1.04 g, 3.44mmol, 5.0 equiv.) or N-hydroxyphenylpyruvylidene-alaninatoaquocopper(II) complex (1.35 g, 4.2 mmol, 6.0 equiv.) in pyridine (40 ml) andtriethylamine was added via syringe in sequence under N₂. The solutionmixture was stirred for a period of 2 4 h at ambient temperature.Unreacted copper complex partially suspended in the solution wasremoved. It was added hexane (100 ml) to effect precipitation of solidproducts. The solid precipitates were isolated by centrifuge, washedwith hexane (50 ml), and dried in vaccuo. It was further washed twice bywater, brine, and CH₃CN (20 ml each) and dried in vaccuo to afford brownsolids of1-dimethyl-3-hydroxyphenylmethyl-fulleropyrrolidine-1,3-dicarboxylatoaquocopper(II) complex (665 mg).

[0047] Brown solids of1-dimethyl-3-hydroxyphenylmethyl-fulleropyrrolidine-1,3-dicarboxylato-aquocopper(II) complex (0.5 g) were dissolved in a mixture of pyridine (25 ml) andwater (25 ml) or o-dichlorobenzene EtOH. It was stirred in the presenceof Dowex acid resin (50WX8, 2.0 g) for a period of 4.0 h. The solidresin was filtered off. The remaining solution was stirred further withfresh Dowex acid resin (50WX8, 1.5 g) for an additional 30 min. At theend of the ion exchanging reaction, Dowex resin was filtered. Aftersolvent evaporation of the filtrate, the resulting dark solids werewashed with ethanol and dried in vaccuo to give the product of1-dimethyl-3-hydroxyphenylmethyl-fulleropyrrolidine-1,3-dicarboxylicacid. IR max (KBr) 3430 (br, s), 2933 (w), 2866, 1659 (s), 1620, 1517,1442, 1364, 1321, 1237, 1175, 1112, 821, and 528. Treatment of1-dimethyl-3-hydroxyphenylmethyl-fulleropyrrolidine-1,3-dicarboxylicacid with dil. HCl (2.0 N) gave the corresponding N-protonated1,3-dimethyl-fulleropyrrolidine-1,3-dicarboxylic acid containing freecarboxylic acids. IR_(max) (KBr) 3401 (br, s), 3230, 2933, 2851, 28002500 (br, CO₂H), 1758, 1718, 1646 (s), 1516, 1442, 1363, 1320, 1174,1036, 991, 822, and 504.

EXAMPLE 3 Synthesis of E-isomer of1-dimethyl-3-(3,4-dihydroxyphenyl)methyl-fulleropyrrolidine1,3-dicarboxylic acid

[0048] In a conical flask charged with 3-(3,4-dihydroxyphenyl)-L-alanine(L-DOPA, 1.0 g, 5.1 mmol) and a mixture of water and ethanol (10 ml,2:1) and stirred for a period of 20 min was added pyruvic acid (446 mg,5.1 mmol). The reaction mixture was stirred at 40° C. for 2.0 h. Theresulting yellowish solution was then added copper (II) acetate (1.0 g,5.1 mmol) in water-ethanol (10 ml) and stirred for an additional 2 4 h,causing precipitation of pale blue solids. The solids were filtered,washed with water, ethanol, and dried to yieldN-pyruvylidene-3-(3,4-dihydroxyphenyl)alaninatoaquocopper (II) complex(1.02 g). IR_(max) (KBr) 3412 (br, s), 3251 (br, s), 1615 (s), 1500,1382, 1282, 1251, 1157, 869, 721, and 645.

[0049] To a solution of C₆₀ (100 mg, 0.14 mmol) in o-dichlorobenzene (40ml), N-pyruvylidene-3-(3,4-dihydroxyphenyl)alaninatoaquocopper (II)complex (288 mg, 0.84 mmol, 6.0 equiv.) in pyridine (35 ml) was addedvia syringe under N₂. The solution mixture was stirred for a period of15 h at 50-60° C. It was added hexane (100 ml) to effect precipitationof solid products. The solid precipitates were isolated by centrifuge,washed with hexane (50 ml), and dried in vaccuo. It was further washedtwice by water, brine, and CH₃CN (20 ml each) and dried in vaccuo toafford dark brown solids of1-dimethyl-3-(3,4-dihydroxyphenyl)methyl-fulleropyrrolidine-1,3-dicarboxylato-aquocopper(II) complex (150 mg).

[0050] Brown solids of1-dimethyl-3-(3,4-dihydroxyphenyl)methyl-fulleropyrrolidine-1,3-dicarboxyl-atoaquocopper(II) complex (150 mg) were dissolved in a mixture of pyridine (20 ml)and water (20 ml). It was stirred in the presence of Dowex acid resin(50WX8, 1.0 g) for a period of 2.0 h. The solid resin was filtered off.The remaining solution was stirred further with fresh Dowex acid resin(50WX8, 1.0 g) for an additional 30 min. At the end of the ionexchanging reaction, Dowex resin was filtered. After solvent evaporationof the filtrate, the resulting dark solids were washed with ethanol anddried in vaccuo to give the product of1-dimethyl-3-(3,4-dihydroxyphenyl)methyl-fulleropyrrolidine-1,3-dicarboxylicacid (200 mg). IR_(max) (KBr) 3395 (br, s), 2950 (w), 2922 (w),2800-2500 (br), 1613, 1545, 1470, 1427, 1302, 1187, 1162, 1067 (w), 862,701 (w), 625 (w), and 525.

EXAMPLE 4 Synthesis of E-isomer of fulleropyrrolidine-1,3-di(3-propanoicacid)-1,3-dicarboxylic acid

[0051] In a conical flask charged with L-glutamic acid (1.47 g, 10.0mmol) and a mixture of water and ethanol (20 ml, 2:1) and stirred for aperiod of 20 min was added 2-ketoglutaric acid (1.46 g, 10.0 mmol). Thereaction mixture was stirred at ambient temperature for a period of 2.0h at pH 6.0 7.0 using NaOH as a titrating agent. The resulting colorlesssolution was then added copper (II) acetate (1.99 g, 10.0 mmol) inwater-ethanol (10 ml) and stirred for an additional 2 h, causingprecipitation of pale blue solids. The solids were filtered, washed withethanol and ether, and dried in vaccuo to yieldN-(₂-ketoglutarylidene)-L-glutamitoaquocopper (II) complex (2.6 g).IR_(max) (KBr) 3439 (br, s), 3282 (br, s), 2949, 2581, 1623 (s), 1392,1343, 1231, 1147, 1095, 939, 676, and 641.

[0052] To a solution of C₆₀ (400 mg, 0.64 mmol) in o-dichlorobenzene(100 ml), N-(₂-ketoglutarylidene)- L-glutamitoaquocopper (II) complex(1.3 g, 6.0 equiv.) in pyridine (50 ml) was added via syringe under N₂.The solution mixture was stirred in the presence of1,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 300 mg) for a period of 5 h atambient temperature. At the end of reaction, hexane (100 ml) was addedto the reaction mixture causing precipitation of solid products. Thesolid precipitates were isolated by centrifuge, washed with hexane (50ml), and dried in vaccuo. It was further washed twice by water, brine,and CH₃CN (20 ml each) and dried in vaccuo to afford dark brown solidsof fulleropyrrolidine-1,3-di(3-propanoicacid)-1,3-dicarboxylato-aquocopper (II) complex. It was then dissolvedin DMSO (30 ml) and treated with Dowex acid resin (50WX8, 1.0 g) for aperiod of 2.0 h. The solid resin was filtered off. The remainingsolution was stirred further with fresh Dowex acid resin (50WX8, 1.0 g)for an additional 30 min. At the end of the ion exchanging reaction,Dowex resin was filtered. Solid products were precipitated from thefiltrate by addition of a mixture of ether and acetone. The precipitateswere washed with ether and acetone and dried in vaccuo to give brownsolids of fulleropyrrolidine-1,3-di(3-propanoic acid)-1,3-dicarboxylicacid (550 mg). IR_(max) (KBr) 3422 (br, s), 2928 (w), 2857 (w), 1716,1635 (s), 1435, 1371, 1200 (w), 1018, 952, and 527. Treatment offulleropyrrolidine-1,3 di(3-propanoic acid)-1,3-dicarboxylic acid withdil. HCl (2.0 N) gave the corresponding N-protonatedfulleropyrrolidine-1,3-di(3-propanoic acid)-1,3-dicarboxylic acidcontaining free carboxylic acids. IR_(max) (KBr) 3433 (br, s), 2928,2853, 2800 2500 (br, CO₂H), 1792 (w), 1721 (s), 1630 (s), 1440, 1411,1328, 1184, 1004, 949, 764, and 526.

EXAMPLE 5 Synthesis of E-isomer of1-methyl-3-thiomethyl-fulleropyrrolidine-1,3-dicarboxylic acid

[0053] In a conical flask charged with L-cysteine (1.21 g, 10.0 mmol)and a mixture of water and ethanol (20 ml, 2:1) and stirred for a periodof 20 min was added pyruvic acid (880 mg, 10.0 mmol). The reactionmixture was stirred at ambient temperature for a period of 1.0 h. Theresulting colorless solution was then added copper (II) acetate (1.99 g,10.0 mmol) in water-ethanol (10 ml) and stirred for an additional 2 h,causing precipitation of dark gray solids. The solids were filtered,washed with ethanol and ether, and dried in vaccuo to yieldN-pyruvylidene-L-cysteinatoaquocopper (II) complex (1.6 g). IR_(max)(KBr) 3447 (br), 3221 (br), 2994 (w), 2935 (w), 1666, 1625, 1598 (s),1574 (s), 1423, 1404, 1378, 1315, 1178, 1016, 970, 937, 884, 759, 713,and 642.

[0054] To a solution of C₆₀ (400 mg, 0.64 mmol) in o-dichlorobenzene(100 ml), N-pyruvylidene-L-cysteinatoaquocopper (II) complex (600 mg,6.0 equiv.) in pyridine (30 ml) was added via syringe under N₂. Themixture was stirred for a short period of 10 min at ambient temperatureto give a solution containing suspended brown solids. At the end ofreaction, hexane (100 ml) was added to effect complete precipitation ofsolid products. The solid precipitates were isolated by centrifuge,washed with hexane (50 ml), and dried in vaccuo. It was then dissolvedin a mixture of o-dichlorobenzene and ethanol (1:1, 40 ml) and treatedwith Dowex acid resin (50WX8, 1.0 g) for a period of 2.0 h. The solidresin was filtered off. The remaining solution was stirred further withfresh Dowex acid resin (50WX8, 1.0 g) for an additional 30 min. At theend of the ion exchanging reaction, Dowex resin was filtered. Ethanolwas removed from the filtrate and solid products were precipitated byaddition of ether to the remaining liquid. The precipitates were washedwith ether and dried in vaccuo to give brown solids of1-methyl-3-thiomethyl-fulleropyrrolidine-1,3-dicarboxylic acid (520 mg).IR_(max) (KBr) 3429 (br, s), 2979 (w), 2935 (w), 1721, 1631 (s), 1540(w), 1377, 1232, 1180, 955 (w), 767, and 525.

EXAMPLE 6 Synthesis of E-isomer of1-methyl-3-hydroxymethyl-fulleropyrrolidine-1,3-dicarboxylic acid

[0055] In a conical flask charged with L-serine (1.19 g, 10.0 mmol) anda mixture of water and ethanol (20 ml, 2:1) and stirred for a period of20 min was added pyruvic acid (880 mg, 10.0 mmol). The reaction mixturewas stirred at ambient temperature for a period of 2.0 h. The resultingcolorless solution was then added copper (II) acetate (1.99 g, 10.0mmol) in water-ethanol (10 ml) and stirred for an additional 2 h,causing precipitation of pale blue solids. The solids were filtered,washed with ethanol and ether, and dried in vaccuo to yieldN-pyruvylidene-L-serinatoaquocopper (II) complex (1.7 g). IR_(max) (KBr)3369 (br, s), 2988 (w), 1731, 1625 (s), 1398, 1341, 1222, 1199, 1145(w), 1106, 1073,957 (w), 894, 857, 723, 648, and 589.

[0056] To a solution of C₆₀ (400 mg, 0.64 mmol) in o-dichlorobenzene(100 ml), N-pyruvylidene-L-serinatoaquocopper (II) complex (590 mg, 6.0equiv.) in pyridine (30 ml) was added via syringe under N₂. The mixturewas stirred in the presence of triethylamine for a period of 12 h atambient temperature to give a solution containing suspended brownsolids. At the end of reaction, hexane (100 ml) was added to effectcomplete precipitation of solid products. The solid precipitates wereisolated by centrifuge, washed with hexane (50 ml), and dried in vaccuo.It was then dissolved in a mixture of o-dichlorobenzene and ethanol(1:1, 40 ml) and treated with Dowex acid resin (50WX8, 1.0 g) for aperiod of 2.0 h. The solid resin was filtered off. The remainingsolution was stirred further with fresh Dowex acid resin (50WX8, 1.0 g)for an additional 30 min. At the end of the ion exchanging reaction,Dowex resin was filtered. Ethanol was removed from the filtrate andsolid products were precipitated by addition of ether to the remainingliquid. The precipitates were washed with ether and dried in vaccuo togive brown solids of1-methyl-3-hydroxymethyl-fulleropyrrolidine-1,3-dicarboxylic acid (500mg). IR_(max) (KBr) 3445 (br, s), 2926 (w), 2853 (w), 1786, 1729, 1633(s), 1454 (w), 1381, 1168, 1107, 1076, 1042, and 533. Treatment of1-methyl-3-hydroxymethyl-fulleropyrrolidine-1,3-dicarboxylic acid withdil. HCl (2.0 N) gave the corresponding N-protonated1-methyl-3-hydroxymethyl-fulleropyrrolidine-1,3-dicarboxylic acidcontaining free carboxylic acids. IR_(max) (KBr) 3421 (br, s), 3211,2954, 2800 2500 (br, CO₂H), 1762, 1719 (CO₂H), 1630 (s), 1428 (w), 1380,1183, 1112 (w), 1036 991, 928 (w), 755 (w), 625 (w), and 526.

EXAMPLE 7 Synthesis of E-isomer of1-isobutyl-3-(o-hydroxyphenyl)-fulleropyrrolidine1-carboxylic acid

[0057] In a conical flask charged with L-leucine (2.44 g, 20.0 mmol) anda mixture of water and ethanol (20 ml, 2:1) and stirred for a period of20 min was added salicylaldehyde (2.62 g, 20.0 mmol). The reactionmixture was stirred at 50° C. for a period of 5.0 h at pH 7.0 using NaOHas a titrating agent. The resulting pale yellow solution was then addedcopper (II) acetate (4.0 g, 20.0 mmol) in water-ethanol (10 ml) andstirred for an additional 30 min, causing precipitation of paleblue-green solids. The solids were filtered, washed with ethanol andether, and dried in vaccuo to yieldN-(2-hydroxybenzylidene)-L-leucinatoaquocopper (II) complex (4.5 g).IR_(max) (KBr) 3383 (br, w), 3322 (br, w), 3252 (br, w), 2961, 2912,2875, 1649 (s), 1628, 1606, 1528,1451, 1336, 1198, 1147, 1079 (w), 861(w), 802, 767, 730, and 564.

[0058] To a solution of C₆₀ (1.0 g, 1.3 mmol) in o-dichlorobenzene (300ml), N-(₂-hydroxybenzylidene)-L-leucinatoaquocopper (II) complex (1.64g, 5.2 mmol, 4.0 equiv.) in pyridine (100 ml) was added via syringeunder N₂. The mixture was stirred in the presence of1,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 1.0 g) for a period of 15 h atambient temperature to give a solution containing suspended brownsolids. At the end of reaction, hexane (100 ml) was added to effectcomplete precipitation of solid products. The solid precipitates wereisolated by centrifuge, washed with hexane (50 ml), and dried in vaccuo,yielding 1.4 g of products. It was then dissolved in a mixture oftoluene and ethanol (9:1, 100 ml, brown solution) and treated with Dowexacid resin (50WX8, 2.0 g) for a period of 2.0 4.0 h. The solid resin wasfiltered off. The remaining solution was stirred further with freshDowex acid resin (50WX8, 1.5 g) for an additional 30 min. At the end ofthe ion exchanging reaction, Dowex resin was filtered. Solvent wasremoved from the filtrate and resulting solid products were washed withhexane and dried in vaccuo to give brown solids of1-isobutyl-3-(o-hydroxyphenyl)-fulleropyrrolidine-1-carboxylic acid (900mg). R_(f) 0.35 (thin layer chromatography, SiO₂, toluene-ethanol/9:1);IR_(max) (KBr) 3440 (br, s), 2957, 2929, 2866, 1706, 1619, 1575, 1495(w), 1446, 1387 (w), 1293 (w), 1252, 1228, 1179, 1155, 1043, and 650;m/z 955 (M+).

EXAMPLE 8 Synthesis of E-isomer of1-methyl-3-ethyl-3′-(o-hydroxyphenyl)-fulleropyrrolidine-1-carboxylicacid.

[0059] Into a conical flask charged with L-alanine (1.78 g, 20.0 mmol),molecular sieves (4Å), and ethanol (20 ml) was added2-hydroxypropiophenone (3.0 g, 20.0 mmol). The reaction mixture wasstirred at the reflux temperature for a period of 24.0 h at pH 8.0 usingNaOH as a titrating agent. The resulting yellow solution was then addedcopper (II) acetate (4.0 g, 20.0 mmol) in water-ethanol (15 ml, 2:1) andstirred for an additional 2.0 h, causing precipitation of green solids.The solids were filtered, washed with ethanol and ether, and dried invaccuo to yield N-(2-hydroxypropiophenonylidene)-L-alainatoaquocopper(II) complex (4.0 g). IR_(max) (KBr) 3470 (br, w), 3305, 3245, 2981,2933, 2880,1622 (s), 1575, 1465, 1401, 1363, 1298, 1142, 1125, 1076,1028, 928, 857, 788, 709, 672, 618, and 575.

[0060] To a solution of C₆₀ (300 mg, 0.4 mmol) in o-dichlorobenzene (100ml), N-(2-hydroxypropiophenonylidene)-L-alainatoaquocopper (II) complex(590 mg, 1.8 mmol, 4.5 equiv.) in pyridine (30 ml) was added via syringeunder N₂. The mixture was stirred in the presence of triethylamine (0.5ml) for a period of 24 h at ambient temperature to give a solutioncontaining suspended brown solids. At the end of reaction, hexane (50ml) was added to effect complete precipitation of solid products. Thesolid precipitates were isolated by centrifuge, washed with hexane (30ml), and dried in vaccuo. It was then dissolved in a mixture ofo-dichlorobenzene and ethanol (1:1, 40 ml) and treated with Dowex acidresin (50WX8, 1.0 g) for a period of 2.0 h. The solid resin was filteredoff. The remaining solution was stirred further with fresh Dowex acidresin (50WX8, 1.0 g) for an additional 30 min. At the end of the ionexchanging reaction, Dowex resin was filtered. Solvent was removed fromthe filtrate and resulting solid products were washed with hexane CH₃CNand dried in vaccuo to give brown solids of1-methyl-3-ethyl-3′-(o-hydroxyphenyl)-fulleropyrrolidine-1-carboxylicacid (310 mg). IR_(max) (KBr) 3435 (br, s), 3089, 2933, 1722 (w), 1625(s), 1520 (w), 1413, 1364, 1308, 1168, 1118 (s), 1037 (s), 1010 (s),677, and 528. Treatment of1-methyl-3-ethyl-3′-(o-hydroxyphenyl)-fulleropyrrolidine-1-carboxylicacid with dil. HCl (2.0 N) gave the corresponding N-protonatedderivative containing free carboxylic acids. IR_(max) (KBr) 3427 (br,s), 2950, 2800-2500 (br, CO₂H), 1726 (CO₂H), 1637 (s), 1514,1418 (w),1258 (w), 1205, 1119, 1038, and 612.

EXAMPLE 9 Synthesis of E-isomer of1-methyl-3-(2,3,4-trihydroxyphenyl)-fulleropyrrolidine-1-carboxylicacid.

[0061] In a conical flask charged with L-alanine (0.98 g, 10.0 mmol) anda mixture of water and ethanol (20 ml, 2:1) and stirred for a period of10 min was added 2.3.4-trihydroxybenzaldehyde (1.54 g, 10.0 mmol). Thereaction mixture was stirred at 40° C. for a period of 2.0 h. Theresulting yellow solution was then added copper (II) acetate (2.0 g,10.0 mmol) in water-ethanol (5.0 ml) and stirred for an additional 30min, causing precipitation of dark green solids. The solids werefiltered, washed with ethanol and ether, and dried in vaccuo to yieldN-(2.3.4-trihydroxybenzylidene)-L-alainnatoaquocopper (II) complex (1.95g). IR_(max) (KBr) 3322 (br), 3248 (br), 2919, 2853, 1574 (s), 1484,1443, 1399, 1320, 1278, 1187 (w), 1098, 1041 (w),791, 731, 671, and 519.

[0062] To a solution of C₆₀ (300 mg, 0.4 mmol) in o-dichlorobenzene (100ml), N-(2.3.4-trihydroxybenzylidene)-L-alainnatoaquocopper (II) complex(630 mg, 2.0 mmol, 5.0 equiv.) in pyridine (30 ml) was added via syringeunder N₂. The mixture was stirred for a period of 15 h at ambienttemperature to give a solution containing suspended brown solids. At theend of reaction, hexane (50 ml) was added to effect completeprecipitation of solid products. The solid precipitates were isolated bycentrifuge, washed with hexane (30 ml), and dried in vaccuo. It was thendissolved in a mixture of o-dichlorobenzene and ethanol (1:1, 40 ml) andtreated with Dowex acid resin (50WX8, 1.0 g) for a period of 2.0 h. Thesolid resin was filtered off. The remaining solution was stirred furtherwith fresh Dowex acid resin (50WX8, 1.0 g) for an additional 30 min. Atthe end of the ion exchanging reaction, Dowex resin was filtered.Solvent was removed from the filtrate and solids were precipitated byaddition of diethylether. The solid precipitates were washed with hexaneand dried in vaccuo to give brown solids of1-methyl-3-(2,3,4-trihydroxyphenyl)-fulleropyrrolidine-1-carboxylic acid(290 mg). IR_(max) (KBr) 3422 (br, s), 2972, 2927, 2846, 1706 (w), 1635(s), 1447, 1374, 1314, 1162, 1013, 951, and 526. Treatment of1-methyl-3-(2,3,4-trihydroxyphenyl) -fulleropyrrolidine-1-carboxylicacid with dil. HCl (2.0 N) gave the corresponding N-protonatedderivative containing free carboxylic acids. IR_(max) (KBr) 3420 (br,s), 3245 (br), 2978 (w), 2932 (w), 2857 (w), 2800-2500 (br, CO₂H), 1709(CO₂H), 1636 (s), 1448, 1403, 1178, 1129, 1037, 1011, 952, and 527.

EXAMPLE 10 Synthesis of1,3-dimethyl-N-(p-bromobenzyl)fulleropyrrolidine-1,3-dicarboxylicanhydride.

[0063] To a solution of 1,3-dimethyl-fulleropyrrolidine-1,3-dicarboxylicacid (220 mg, 0.25 mmol) in a mixture of o-dichlorobenzene and DMSO(6:1, 50 ml), phosphorous pentaoxide (250 mg) was added under N₂. Themixture was stirred at 50° C. for a period of 12.0 h to effectdehydrative anhydride formation. At the end of reaction, the insolublesolids were separated by centrifuge. The remaining solution wastransferred via syringe into the second reaction flask containingp-bromobenzyl chloride (66 mg, 0.3 mmol) and triethylamine (0.1 ml). Themixture was stirred at 50° C. for an additional 8.0 h under N₂. Diethylether (50 ml) was then added to effect complete precipitation of solidproducts. The solid precipitates were isolated by centrifuge, washedwith diethyl ether (30 ml), water, ethanol, and diethyl ether insequence and dried in vacuo to give brown solids of1,3-dimethyl-N-(p-bromobenzyl)fulleropyrrolidine-1,3-dicarboxylicanhydride (180 mg). ¹H NMR (two amide isomers in an equal amount) 1.14(s, 6H), 1.24 (s, 6H), 7.75 (dd, 4H), 8.15 (dd, 4H); IR_(max) (KBr) 3402(br, s), 2984, 2925, 1787 (w), 1737 (s), 1630, 1591, 1513 (w), 1399,1255, 1173, 1094, 1071, 1008, 751, and 527.

EXAMPLE 11 Synthesis ofoligo[1,3-dimethyl-fulleropyrrolidine-1,3-dicarboxylic N-amide].

[0064] To a solution of 1,3-dimethyl-fulleropyrrolidine-1,3-dicarboxylicacid (220 mg, 0.25 mmol) in a mixture of o-dichlorobenzene and DMSO(6:1, 50 ml), phosphorous pentaoxide (250 mg) was added under N₂. Themixture was stirred at 50° C. for a period of 12.0 h to effectdehydrative anhydride formation. At the end of reaction, the insolublesolids were separated by centrifuge. The remaining solution wastransferred via syringe under N₂ into the second reaction flaskcontaining 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 1.0 g). The mixturewas stirred at 100° C. for an additional 24.0 h under N₂ to afford adark brown-black solution. Diethyl ether (50 ml) was then added toeffect complete precipitation of solid products. The solid precipitateswere isolated by centrifuge, washed twice with diethyl ether (30 ml),ethanol, and diethyl ether in sequence. It was treated with dil HCl (2N) in THF, washed with THF, and dried in vaccuo. to give dark brownsolids of oligo[1,3-dimethyl-fulleropyrrolidine-1,3-dicarboxylicN-amide] (165 mg). IR_(max) (KBr) 3402 (br, s), 2931, 2861, 1712 (w),1661 (s), 1613, 1442, 1372, 1324, 1156 (s), 1036 (s), 990, 675, and 611.

EXAMPLE 12 Synthesis of1,3-dimethyl-N-succinamitofulleropyrrolidine-1,3-dicarboxylic acid,C₆₀[C(CH₃)CO₂H]₂NCO-CH₂CH₂CO₂H.

[0065] To a solution of 1,3-dimethyl-fulleropyrrolidine-1,3-dicarboxylicacid (440 mg, 0.5 mmol) in a mixture of o-dichlorobenzene and DMSO (6:1,80 ml), succinic anhydride (100 mg) and1,8-diazabicyclo[5.4.0]undec-7-ene (DBU, 1.0 g ) were added under N₂.The mixture was stirred at 30° C. for a period of 4.0 h. At the end ofreaction, the solution was treated with dil. HCl (2.0 N). Diethyl ether(50 ml) was then added to effect complete precipitation of solidproducts. The solid precipitates were isolated by centrifuge, washedtwice with diethyl ether (30 ml), water, and diethyl ether in sequenceand dried in vaccuo. to give dark brown solids of1,3-dimethyl-N-succinamitofulleropyrrolidine-1,3-dicarboxylic acid (480mg). IR_(max) (KBr) 3426 (br, s), 2930, 2595 (br, CO₂H), 1752 (w), 1718(s, CO₂H), 1626, 1402, 1180, 1086, 1000, 773 (w), 653 (w), and 525 (w).

EXAMPLE 13 Synthesis oftris(hexadecaanilino)-1,3-dimethyl-N-succinamitofulleropyrrolidine-1,3-dicarboxylate,C₆₀[C(CH₃)CO—(NH—C₆H₄—N═C₆H₄═N—C₆H₄—NH—C₆H₄—)₄—H]₂NCO—CH₂CH₂CO—(NH—C₆H₄—N═C₆H₄═N—C₆H₄—NH—C₆H₄—)₄—H

[0066] To a solution of1,3-dimethyl-N-succinamito-fulleropyrrolidine-1,3-dicarboxylic acid,C₆₀[C(CH₃)CO₂H]₂NCO—CH₂CH₂CO₂H, (498 mg, 0.5 mmol) in a mixture ofo-dichlorobenzene and DMSO (6:1, 100 ml), hexadecaaniline (emeraldinebase form, 2.2 g, 1.5 mmol), 1,3-dicyclohexylcarbodiimide (DCC, 340 mg,1.65 mmol), and 1-hydroxybenzotriazole (BtOH, 223 mg, 1.65 mmol) wereadded under N₂. The mixture was stirred at 40° C. for a period of 24.0h. At the end of reaction, the solution was added diethyl ether (100 ml)to effect complete precipitation of solid products. The solidprecipitates were isolated by centrifuge, treated with aqueous NH₄OH,washed twice with water and diethyl ether and dried in vaccuo. to givedark blue solids oftris(hexadecaanilino)-1,3-dimethyl-N-succinamitofulleropyrrolidine-1,3-dicarboxylate(2.5 g). IR_(max) (KBr) 3433 (br, s), 3284, 2932 (w), 2859 (w), 1596,1506 (s), 1305, 1252, 1150, 822, 749, 696, and 506.

EXAMPLE 14 Synthesis oftris(glycylglycyl)-1,3-dimethyl-N-succinamitofulleropyrrolidine1,3-dicarboxylate,C₆₀[C(CH₃)CO—(NHCH₂CO—NHCH₂CO₂H]₂NCO—CH₂CH₂CO—NHCH₂CO—NHCH₂CO₂H.

[0067] To a solution of1,3-dimethyl-N-succinamito-fulleropyrrolidine-1,3-dicarboxylic acid,C₆₀[C(CH₃)CO₂H]₂NCO—CH₂CH₂CO₂H, (498 mg, 0.5 mmol) in a mixture ofo-dichlorobenzene and DMSO (6:1, 100 ml), glycylglycine (198 mg, 1.5mmol), 1,3-dicyclohexylcarbodiimide (DCC, 340 mg, 1.65 mmol), and1-hydroxybenzotriazole (BtOH, 223 mg, 1.65 mmol) were added under N₂.The mixture was stirred at 40° C. for a period of 24.0 h. At the end ofreaction, the solution was added diethyl ether (100 ml) to effectcomplete precipitation of solid products. The solid precipitates wereisolated by centrifuge, treated with dil. HCl (2.0 N), washed twice withwater and diethyl ether and dried in vaccuo. to give dark brown solidsoftris(glycylglycyl)-1,3-dimethyl-N-succinamitofulleropyrrolidine-1,3-dicarboxylate(480 mg). IR_(max (KBr)) 3431 (br, s), 2929, 2860 (w), 1773, 1701, 1654(s), 1550, 1391, 1227, 1178, 1056 (w), 999 (w), and 527.

EXAMPLE 15 Detection of High Free Radical Scavenging Potency ofHydrophilic Fullerene Derivatives

[0068] The xanthine/xanthine oxidase enzymatic system is highlyeffective for the production of superoxide radicals (O₂). Reaction ofsuperoxide radicals with cytochrome (Fe⁺³) C may result in a product ofreduced cytochrome (Fe⁺²) C which shows a respectable optical absorptionat 550 nm. Therefore, the detected optical absorption intensity of thereduced cytochrome (Fe⁺²) C can be correlated to the quantity ofsuperoxide radicals reacted with cytochrome (Fe⁺³) C. Scavenging ofsuperoxide radicals by hydrophilic fullerene derivatives in thebio-medium inhibits the formation of reduced cytochrome (Fe⁺²) C andthus reduce the optical absorption at 550 nm.

[0069] In one experiment, xanthine (50 M) was added to a physiologicalmedium (3 ml) containing cytochrome C(10 M), ethylenediaminetetraaceticacid (EDTA) (10 mM) and a phosphate buffer (50 mM) at pH 7.8. Themixture was then added xanthine oxidase in quantity enough to induce0.025 unit of optical absorption at 550 nm per 5 min (Mc Cord, et al. J.Biol. Chem. 1969, 244, 6049.). Subsequently,1,3-dimethyl-N-succinamitofulleropyrrolidine-1,3-dicarboxylic acid,C₆₀[C(CH₃)CO₂H]₂NCO—CH₂CH₂CO₂H, prepared in Example 12, in aconcentration of 0, 5.0, 10.0, 25.0, 50, and 100 M was added inseparated runs while the absorption intensity of the reduced cytochromeC was recorded. A rapid decrease of reduced cytochrome C to roughly 50%and 20% of the control value was obtained with the dose of1,3-dimethyl-N-succinamitofulleropyrrolidine-1,3-dicarboxylic acid as 25and 100 M, respectively. These results substantiated efficientscavenging of superoxide radicals by1,3-dimethyl-N-succinamitofulleropyrrolidine-1,3-dicarboxylic acid thatled to the inhibition of cytochrome C reduction.

EXAMPLE 16

[0070] The growth inhibitory effect of1,3-dimethyl-N-succinamitofulleropyrrolidine-1,3-dicarboxylic acid,C₆₀[C(CH₃)CO₂H]₂NCO—CH₂CH₂CO₂H, which was prepared as described inExample 12, on fibrosarcoma tumor cells upon photo-irradiation wasstudied in vitro. Fibrosarcoma tumor cells (0.5 ml, 4×10⁴/ml, CCRC60037) were grown in the MEM medium in a 24-well plate for a period of24 h. It was treated by1,3-dimethyl-N-succinamitofulleropyrrolidine-1,3-dicarboxylic acid in aconcentration of 0.0, 2.5, 5.0, 7.5, and 10.0 M for a period of 24hours. The MEM medium was removed and replaced by the fresh medium (1.0ml). The cell-containing plates were exposed to a fluorescence lightsource (27 W) in a distance of 5-6 cm for a period of 10, 20, 40, and 60min. The plates were then kept in incubator at 37° C. a period of 48 h.Measurement of cell viability in each plate was performed by the MTTassay using optical absorption at 540 nm. The data indicated a rapiddecrease in the tumor cell count under application of1,3-dimethyl-N-succinamitofulleropyrrolidine-1,3-dicarboxylic acid in aconcentration of only 2.5 M with a photo-irradiation period of more than20 min. These results substantiated high efficacy of the growthinhibition on fibrosarcoma tumor cells upon photo-irradiation.

Other Embodiments

[0071] From the above description, one skilled in the art can easilyascertain the essential characteristics of the present invention, andwithout departing from the spirit and scope thereof, can make variouschanges and modifications of the invention to adapt it to various usagesand conditions. Thus, other embodiments are also within the claims.

What is claimed is:
 1. A compound of formula (I):

wherein F_(f) is F(—K)_(m)(—Y—Z)_(q) in which F is a fullerene core; each K, independently, is —OH, —SH, —NH₂, —NHOH, —SO₃H, —OSO₃H, —CO₂H, —CONH₂, —CONHNH₂, —P(OH)₃, —PO(OH)₂, —O—PO(OH)₂, —O—PO(OH)—O—PO(OH)₂, 13 O—PO(O⁻)—O—CH₂CH₂—NH₃ ⁺, —O—PO(O⁻)—O—CH₂CH₂—N⁺ (CH₃)₃, -glycoside, —OCH₃, —OCH₂(CHOH)₄—CH₂OH, —OCH₂(CHOH)₂—CH₂OH, —NH—CH₂—CO₂H, —[CH(CO₂H)—CH₂]₁₋₁₀₀—OH, —[CH(CO₂R^(a))—CH₂]₁₋₁₀₀—OH, —[C(CH₃)(CO₂H)—CH₂]₁₋₁₀₀—OH, —[C(CH₃)(CO₂ R^(a))—CH₂]₁₋₁₀₀—OH, —N(OH)₂, —NH₃ ⁺, —N⁺H₂R^(a), —N⁺HR^(a)R^(b), or —N⁺R^(a)R^(b)R^(c); each Y is —A—B—, in which A is —O—, —NH—, —S—, —CO—O—, —O—CO—, —O—CO—O—, —O—CO—NH—, —NH—CO—NH—, —CO—NH—, or —NH—CO—; and, B is —R^(a)—O—[Si(CH₃)₂—O—]₁₋₁₀₀, C₁₋₂₀₀₀ alkyl, C₆₋₄₀ aryl, C₇₋₂₀₀₀ alkylaryl, C₇₋₂₀₀₀ arylalkyl, (C₁₋₃₀ alkyl thioether)₁₋₁₀₀, (C₆₋₄₀ aryl thioether)₁₋₁₀₀, (C₇₋₂₀₀₀ alkylaryl ether)₁₋₁₀₀, (C₇₋₂₀₀₀ arylalkyl ether)₁₋₁₀₀, (C₁₋₃₀ alkyl thioether)₁₋₁₀₀, (C₆₋₄₀ aryl thioether)₁₋₁₀₀, (C₇₋₂₀₀₀ aryl alkylaryl thioether)₁₋₁₀₀, (C₇₋₂₀₀₀ arylalkyl thioether)₁₋₁₀₀, (C₂₋₅₀ alkyl ester)₁₋₁₀₀, (C₇₋₂₀₀₀ ester)₁₋₁₀₀, (C₈₋₂₀₀₀ alkylaryl ester)₁₋₁₀₀, (C₈₋₂₀₀₀ arylalkyl ester)₁₋₁₀₀, —R^(a)—CO—O—(C₁₋₃₀ alkyl ether)₁₋₁₀₀, —R^(a)—CO—O—(C₆₋₄₀ aryl ether)₁₋₁₀₀, —R^(a)CO—O—(C₇₋₂₀₀₀ alkylaryl ester) ₁₋₁₀₀, —R^(a)—CO—O—(C₇₋₂₀₀₀ arylalkyl ether)₁₋₁₀₀, (C₄₋₅₀ alkyl urethane)₁₋₁₀₀, (C₁₄₋₆₀ aryl urethane)₁₋₁₀₀, (C₁₀₋₂₀₀₀ alkylaryl urethane)₁₋₁₀₀, (C₁₀₋₂₀₀₀ arylalkyl urethane)₁₋₁₀₀, (C₅₋₅₀ alkyl urea)₁₋₁₀₀, (C₄₋₆₀ aryl urea)₁₀₀, (C₁₀₋₁₂₀₀₀ alkylaryl urea)₁₋₁₀₀, (C₁₀₋₂₀₀₀ arylalkyl urea)₁₋₁₀₀, (C₂₋₅₀ alkyl amide) ₁₀₋₂₀₀₀ (C₇₋₆₀ aryl amide)₁₋₁₀₀, (C₈₋₂₀₀₀ alkylaryl amide)₁₋₁₀₀, (C₈₋₂₀₀₀ arylalkyl amide)₁₋₁₀₀, (C₃₋₃₀ alkyl anhydride)₁₋₁₀₀, (C₈₋₅₀ aryl anhydride)₁₋₁₀₀, (C₉₋₂₀₀₀ alkylaryl anhydride)₁₋₁₀₀, (C₉₋₂₀₀₀ arylalkyl anhydride)₁₋₁₀₀, (C₂₋₃₀ alkyl carbonate)₁₋₁₀₀, (C₇₋₅₀ aryl carbonate)₁₋₁₀₀, (C₈₋₂₀₀₀ alkylaryl carbonate)₁₋₁₀₀, (C₈₋₂₀₀₀ arylalkyl carbonate)₁₋₁₀₀, —R^(a)—O—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₁₋₃₀ alkyl ether, C₆₋₄₀ aryl ether, C₇₋₂₀₀₀ alkylaryl ether, or C₇₋₂₀₀₀ arylalkyl ether)₁₋₁₀₀, —R^(a)—O—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C²⁻⁵⁰ alkyl ester, C₇₋₆₀ aryl ester, C₈₋₂₀₀₀ alkylaryl ester, or C₈₋₂₀₀₀ arylalkyl ester)₁₋₁₀₀, —R^(a)—O—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₁₋₃₀ alkyl ether, C₆₋₄₀ aryl ether, C₇₋₂₀₀₀ alkylaryl ether, or C₇₋₂₀₀₀ arylalkyl ether)₁₋₁₀₀—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—, —R^(a)—O—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₂₋₅₀ alkyl ester, C₇₋₆₀ aryl ester, C₈₋₂₀₀₀ alkylaryl ester, or C₈₋₂₀₀₀ arylalkyl ester)₁₋₁₀₀—R^(c)—O—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—, R^(a)—NH—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₁₋₃₀ alkyl ether, C₆₋₄₀ aryl ether, C₇₋₂₀₀₀ alkylaryl ether, or C₇₋₂₀₀₀ arylalkyl ether)₁₋₁₀₀, —R^(a)—NH—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO'O—(C₂₋₅₀ alkyl ester, C₇₋₆₀ aryl ester, C₈₋₂₀₀₀ alkylaryl ester, or C₈₋₂₀₀₀ arylalkyl ester)₁₋₁₀₀, —R^(a)—NH—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₁₋₃₀ alkyl ether, C₆₋₄₀ aryl ether, C₇₋₂₀₀₀ alkylaryl ether, or C₇₋₂₀₀₀ arylalkyl ether)₁₋₁₀₀—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—, —R^(a)—NH—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₂₋₅₀ alkyl ester, C₇₋₆₀ aryl ester, C₈₋₂₀₀₀ alkylaryl ester, or C₈₋₂₀₀₀ arylalkyl ester)₁₋₁₀₀—R^(c)—O—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—, —R^(a)—O—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—NH—(C₂₋₅₀ alkyl amide, C₇₋₆₀ aryl amide, C₈₋₂₀₀₀ alkylaryl amide, or C₈₋₂₀₀₀ arylalkyl amide)₁₋₁₀₀, —R^(a)—NH—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—NH—(C₂₋₅₀ alkyl amide, C₇₋₆₀ aryl amide, C₈₋₂₀₀₀ alkylaryl amide, or C₈₋₂₀₀₀ arylalkyl amide)₁₋₁₀₀, or a bond; each Z. independently, is -G-D, wherein G is —R^(a)—, —R^(a)—Ar—, —Ar—R^(a)—, or —AR—; and D is —H, —OH, —SH, —NH₂, —NHOH, —SO₃H, —OSO₃H, —CO₂H, —CONH₂, —CONHNH₂, —CH(NH₂)—CO₂H, —NH—CH₂—CO₂H, —P(OH)₃, —PO(OH)₂, —O—PO(OH)₂, —O—PO(OH)—O—PO(OH)₂, —O—PO(O⁻)—O—CH₂CH₂NH₃ ⁺, —O—PO(O⁻)—O—CH₂CH₂—N⁺ (CH₃)₃, -glycoside, -oligosaccharide, —CO-glycoside, —CO-oligosaccharide, —OCH₃, —OCH₂(CHOH)₄—CH₂OH, —OCH₂(CHOH)₂—CH₂OH, —CO—OCH₂(CHOH)₄—CH₂OH, —C₆H₃(OH)₂, —N(CH₂CO₂H)₂, —CO—N(CH₂CO₂H)₂, —CO—NH—C(CH₂CH₂CO₂H)₃, —CO—NH—C(CH₂CH₂OH)₃, —[CH₂—CH(CO₂R^(a))]₁₋₁₀₀—H, —NH₃ ⁺, —N⁺H₂R^(a), —N⁺HR^(a)R^(b), or —N⁺R^(a)R^(b)R^(c), each of R^(a), R^(b), and R^(c), independently, being C₁₋₂₀ alkyl and Ar being aryl; q is 0-30; and m is 0-30; provided that the sum of q and m is 0-30; each of R¹ and R⁴, independently, is ═O or C₁₋₂₀ hydrocarbon; and each of R² and R⁵, independently, is C₁₋₂₀ hydrocarbon; wherein R¹ and R², or R⁴ and R⁵ can join together to form C₆₋₄₀ aryl which is optionally substituted with halide, —OH, —NHNH₂, —NH₂OH, —NH—CH₂—CO₂H, —CH₂—CH₂-D, —CH₂—B—Z, —CO—CH₂-D, —CO—B—Z, —O—B—Z, or —NH—B—Z; each of B, D, and Z having been defined above; each of R³ and R⁶, independently, is —H, —CH₂-D, —B—Z, -G-E, -G-CO-E, or a side chain of an amino acid; each of B, D, and Z having been defined above, and E being E₁, E₂, or E₃, in which E₁ is Y₁, Y₂-amino, (Y₁, Y₂-alkyl)-amino, Y₁, Y₂-ethylenediamino, (dihydroxymethyl)alkylamino, (X₁, X₃-aryl)amino, or X₁, X₃-aryloxy; E₂ is Y₁, Y₂-alkoxy, (Y₁, Y₂-amino)alkoxy, (Y₁, Y₂, Y₃-aryl)oxy, (dihydroxyalkyl)-aryloxy, (Y₁, Y₂, Y₃-alkyl)amino, (Y₁, Y₂, Y₃-aryl)amino, dihydroxyalkylamino, Y₁, Y₂, Y₃-alkoxy, (trihydroxyalkyl)alkoxy, (trihydroxyalkyl)alkylamino, (dicarboxyalkyl)amino, (Y₁, Y₂, Y₃-alkyl)thio, (X₁, X₃-aryl)thio, (Y₁, Y₂-alkyl)thio, (dihydroxyalkyl)thio, Y₁, Y₂-dioxoalkyl, or tri-(Y₁, Y₂, Y₃-methylaminocarboxyethyl)methylamino; and E₃ is ((glycosidyl)oxoheteroaryl)amino, ((glycosidyl)oxoaryl)amino, (X₁, X₂, X₃-heteroaryl)amino, (X₁-diarylketone)amino, (X, X₁-oxoaryl)amino, (X, X₁-dioxoaryl)amino, (Y₁-alkyl, Y₂-alkyldioxoheteroaryl)amino, (Y₁-alkyl, Y₂-alkyldioxoaryl)amino, (di(Y₁, Y₂-methyl)dioxoheteroaryl)amino, (di(Y₁, Y₂-methyl)dioxoaryl)amino, ((glycosidyl)heteroaryl)amino, ((glycosidyl)aryl)amino, ((carboxylacetylalkyl)oxo-heteroaryl)amino, ((carboxylacetylalkyl)oxoaryl)amino, ((isopropylaminohydroxy-alkoxy)aryl)amino, (X₁, X₂, X₃-alkylaryl)amino, (X₁, X₂, X₃-heteroaryl)oxy, (isopropylaminohydroxyalkyl)aryloxy, (X₁, X₂, X₃-oxoheteroaryl)oxy, (X₁, X₂, X₃-oxoaryl)oxy, (X₁, Y₁-oxoheteroaryl)oxy, (X₁-diarylketone)oxy, (X, X₁-oxoaryl)oxy, (X₁, X₂-dioxoaryl)oxy, (Y₁, Y₂, di-aminodihydroxy)alkyl, (X₁, X₂-heteroaryl)thio, ((tricarboxylalkyl)ethylene-diamino)alkoxy, (X₁, X₂-oxoaryl)thio, (X₁, X₂-dioxoaryl)thio, (glycosidylheteroaryl)thio, (glycosidylaryl)thio, Y₁-alkyl(thiocarbonyl)thio, Y₁, Y₂, -alkyl(thiocarbonyl)thio, Y₁, Y₂, Y₃-alkyl(thiocarbonyl)thio, (Y₁, Y₂-aminothiocarbonyl)thio, (pyranosyl)thio, cysteinyl, tyrosinyl, (phenylalainyl)amino, (dicarboxyalkyl)thio, (aminoaryl)₁₋₁₀₀amino, (pyranosyl)amino, (Y₁-aminoaryl)₁₋₁₀₀amino, (amino(sulfoaryl))₁₋₁₀₀amino, peptidyl, thymidinyl, uridinyl, guanosinyl, adenosinyl, cholesteryl, or biotinylalkoxy; wherein X is halide; each of X₁, X₂, and X₃, independently, is —Y₁, —O—Y₁, —S—Y₁, —NH—Y₁, —CO—O—Y₁, —O—CO—Y₁, —CO—NH—Y₁, —CO—NY₁Y₂, —NH—CO—Y₁, —SO₂—Y₁, —CHY₁Y₂, or —NY₁Y₂; and each of Y₁, Y₂, and Y₃, independently, is —Z or —B—Z; each of x and y, independently, is 0 or 1; and s is 1-6; provided that when x is 0, R¹ is ═O; that when y is 0, R⁴ is ═O; that when x is 1, R¹ and R² join together to form C₆₋₄₀ aryl; and that when y is 1, R⁴ and R⁵ join together to form C₆₋₄₀ aryl; and or a salt thereof.
 2. The compound of claim 1, wherein at least one of x and y is
 1. 3. The compound of claim 2, wherein R¹ and R², or R⁴ and R⁵ can join together to form a benzene ring.
 4. The compound of claim 3, wherein F is C₆₀, C₆₁, C₆₂, C₆₃, C₆₄, C₆₅, C₇₀, C₇₆, C₇₈, C82, C₈₄, or C₉₂, or La@C_(n), Ho@C_(n), Gd@C_(n), or Er@C_(n), in which n is 60, 74, or
 82. 5. The compound of claim 3, wherein the sum of q and m is 0-20.
 6. The compound of claim 3, wherein each K, independently, is —SH, —NHOH, —SO₃H, —OSO₃H, —CONH₂, —CONHNH₂, —P(OH)₃, —PO(OH)₂, —O—PO(OH)₂, —O—PO(OH)—O—PO (OH)₂, —O—PO(O⁻)—O—CH₂CH₂NH₃ ⁺, -glycoside, —O—CH₂—(CHOH)₄—CH₂OH, —O—CH₂(CHOH)₂—CHOH, —N⁺HR^(a)R^(b), or N⁺HR^(a)R^(b)R^(c).
 7. The compound of claim 3, wherein D is —SH, —NHOH, —SO₃H, —OSO₃H, —CONH₂, —CONHNH₂, —P(OH)₃, —PO(OH)₂, —O—PO(OH)₂, —O—PO(OH)—O—PO(OH)₂, —O—PO(O⁻)—O—CH₂CH₂NH₃ ⁺, -glycoside, -oligosaccharide, —CO-glycoside, —CO-oligosaccharide, —O—CH₂—(CHOH)₄—CH₂OH, —O—CH₂—(CHOH)₂—CHOH, —N⁺HR^(a)R^(b), or N⁺HR^(a)R^(b)R^(c).
 8. The compound of claim 3, wherein only one of x and y is
 1. 9. The compound of claim 8, wherein x is 1, y is 0, and R¹ and R² join together to form a benzene ring.
 10. The compound of claim 9, wherein R³ is —H, —B—Z, -G-E, or -G-CO-E.
 11. The compound of claim 9, wherein R⁶ is G-E, G-CO-E, or a side chain of an amino acid.
 12. The compound of claim 13, wherein R⁶ is a side chain of alanine, aspartic acid, cysteine, glutamic acid, phenylalanine, halophenylalanine, hydroxyphenylalanine, glycine, histidine, isoleucine, lysine, leucine, methionine, asparagine, glytamine, arginine, serine, theronine, valine, tryptophan, tyrosine, 2-aminobutyric acid, halophenylalanine, cyclohexylalanine, citrulline, homocitrulline, homoserine, norleucine, norvaline, or ornithine.
 13. The compound of claim 12, wherein R³ is —H, —B—Z, -G-E, or -G-CO-E.
 14. The compound of claim 13, wherein F is C₆₀, and the sum of q and m is 0-20.
 15. The compound of claim 14, said compound is the E-isomer of 1-dimethyl-3-hydroxyphenylmethyl-fulleropyrrolidine-1,3-dicarboxylic acid, 1-dimethyl-3-(3,4-dihydroxyphenyl)methyl-fulleropyrrolidine-1,3-dicarboxylic acid, 1-isobutyl-3-(o-hydroxyphenyl)-fulleropyrrolidine-1-carboxylic acid, 1-methyl-3-ethyl-3′-(o-hydroxyphenyl)-fulleropyrrolidine-1-carboxylic acid, or 1-methyl-3-(2,3,4-trihydroxyphenyl)-fulleropyrrolidine-1-carboxylic acid.
 16. The compound of claim 1, wherein both x and y are
 0. 17. The compound of claim 16, wherein F is C₆₀, C₆₁, C₆₂, C₆₃, C₆₄, C₆₅, C₇₀, C₇₆, C₇₈, C₈₂, C₈₄, or C₉₂, or La@C_(n), Ho@C_(n), Gd@C_(n), or Er@C_(n), in which n is 60, 74, or
 82. 18. The compound of claim 16, wherein the sum of q and m is 0-20.
 19. The compound of claim 16, wherein each K, independently, is —SH, —NHOH, —SO₃H, —OSO₃H, —CONH₂, —CONHNH₂, —P(OH)₃, —PO(OH)₂, —O—PO(OH)₂, —O—POOH)—O—PO(OH)₂, —O—PO(O⁻)—O—CH₂CH₂NH₃ ⁺, -glycoside, —O—CH₂—(CHOH)₄—CH₂OH, —O—CH₂—(CHOH)₂—CHOH, —N⁺HR^(a)R^(b), or N⁺HR^(a)R^(b)R^(c). PO(OH)₂, —O—PO(O⁻)—O—CH₂CH₂NH₃ ⁺, -glycoside, —O—CH₂—(CHOH)₄—CH₂OH, —O—CH₂—(CHOH)₂—CHOH, —N⁺HR^(a)R^(b), or N⁺HR^(a)R^(b)R^(c).
 20. The compound of claim 16, wherein D is —SH, —NHOH, —SO₃H, —OSO₃H, —CONH₂, —CONHNH₂, —P(OH)₃, —PO(OH)₂, —O—PO(OH)₂, —O—PO(OH)—O—PO(OH)₂, —O—PO(O⁻)—O—CH₂CH₂NH₃ ⁺, -glycoside, -oligosaccharide, —CO-glycoside, —CO-oligosaccharide, —O—CH₂—(CHOH)₄—CH₂OH, —O—CH₂—(CHOH)₂—CHOH, —N⁺HR^(a)R^(b), or N⁺HR^(a)R^(b)R^(c).
 21. The compound of claim 16, wherein each of R³ and R⁶, independently, is —B—Z, -G-E, -G-CO-E, or a side chain of alanine, aspartic acid, cysteine, glutamic acid, phenylalanine, halophenylalanine, hydroxyphenylalanine, glycine, histidine, isoleucine, lysine, leucine, methionine, asparagine, glytamine, arginine, serine, theronine, valine, tryptophan, tyrosine, 2-aminobutyric acid, halophenylalanine, cyclohexylalanine, citrulline, homocitrulline, homoserine, norleucine, norvaline, or ornithine.
 22. The compound of claim 21, wherein F is C₆₀, and the sum of q and m is 0-20.
 23. The compound of claim 22, said compound is the E-isomer of 1,3-dimethyl-fulleropyrrolidine-1,3-dicarboxylic acid, fulleropyrrolidine-1,3-di(3-propanoic acid)-1,3-dicarboxylic acid, 1-methyl-3-thiomethyl-fulleropyrrolidine-1,3-dicarboxylic acid, or 1-methyl-3-hydroxymethyl-fulleropyrrolidine-1,3-dicarboxylic acid.
 24. A method for preparing a compound of formula (I):

wherein F_(f) is F(—K)_(m)(—Y—Z)_(q) in which F is a fullerene core; each K, independently, is —OH, —SH, —NH₂, —NHOH, —SO₃H, —OSO₃H, —CO₂H, —CONH₂, —CONHNH₂, —P(OH)₃, —PO(OH)₂, —O—PO(OH)₂, —O—PO(OH)—O—PO(OH)₂, —O—PO(O⁻)—O—CH₂CH₂—NH₃ ⁺, —O—PO(O⁻)—O—CH₂CH₂—N⁺ (CH₃)₃, -glycoside, —OCH₃, —OCH₂(CHOH)₄—CH₂OH, —OCH₂(CHOH)₂—CH₂OH, —NH—CH₂—CO₂H, —[CH(CO₂H)—CH₂]₁₋₁₀₀—OH, —[CH(CO₂R^(a))—CH₂]₁₋₁₀₀—OH, —[C(CH₃)(CO₂H)—CH₂]₁₋₁₀₀—OH, —[C(CH₃)(CO₂R^(a))—CH₂]₁₋₁₀₀OH, —N(OH)₂, —NH₃ ⁺, —N⁺H₂R^(a), —N⁺HR^(a)R^(b), or —N⁺R^(a)R^(b)R^(c); each Y is -A-B—, in which A is —O—, —NH—, —S—, —CO—O—, —O—CO—, —O—CO—O—, —O—CO—NH—, —NH—CO—NH—, —CO—NH—, or —NH—CO—; and B is —R^(a)—O—[Si(CH₃)₂—O—]₁₋₁₀₀, C₁₋₂₀₀₀ alkyl, C₆₋₄₀ aryl, C₇₋₂₀₀₀ alkylaryl, C₇₋₂₀₀₀ arylalkyl, (C₁₋₃₀ alkyl ether)₁₋₁₀₀, (C₆₋₄₀ aryl ether)₁₋₁₀₀, (C₇₋₂₀₀₀ alkylaryl ester)₁₋₁₀₀, (C₇₋₂₀₀₀ arylalkyl ether)₁₋₁₀₀, (C₁₋₃₀ alkyl thioether)₁₋₁₀₀, (C₆₋₄₀ aryl thioether)₁₋₁₀₀, (C₇₋₂₀₀₀ alkylaryl thioether)₁₋₁₀₀, (C₇₋₂₀₀₀ arylalkyl thioether)₁₋₁₀₀, (C₂₋₅₀ alkyl ester)₁₋₁₀₀, (C₇₋₂₀₀₀ aryl ester)₁₋₁₀₀, (C₈₋₂₀₀₀ alkylaryl ester)₁₋₁₀₀, (C₈₋₂₀₀₀ arylalkyl ester)₁₋₁₀₀, —R^(a)—CO—O—(C₁₋₃₀ alkyl ether)₁₋₁₀₀, —R^(a)—CO—O—(C₆₋₄₀ aryl ether)₁₋₁₀₀, —R^(a)—CO—O—(C₇₋₂₀₀₀ alkylaryl ether)₁₋₁₀₀, —R^(a)—CO—O—(C₇₋₂₀₀₀ arylalkyl ether)₁₋₁₀₀, (C₄₋₅₀ alkyl urethane)₁₋₁₀₀, (C₁₄₋₆₀ aryl urethane)₁₋₁₀₀, (C₁₀₋₂₀₀₀ arylalkyl urethane)₁₋₁₀₀, -(C ₁₀₋₂₀₀₀ arylalkylurethane)₁₋₁₀₀, (C₅₋₅₀ alkyl urea)₁₋₁₀₀, (C₁₄₋₆₀ aryl urea)₁₋₁₀₀, (C₁₀₋₂₀₀₀ alkylaryl urea)₁₋₁₀₀, (C₁₀₋₂₀₀₀ arylalkyl urea)₁₋₁₀₀, (C₂₋₅₀ alkyl amide) ₁₋₁₀₀, (C₇₋₆₀ aryl amide)₁₋₁₀₀, (C₈₋₂₀₀₀ alkylaryl amide)₁₋₁₀₀, (C₈₋₂₀₀₀ arylalkyl amide)₁₋₁₀₀, (C₃₋₃₀ alkyl anhydride)₁₋₁₀₀, (C₈₋₅₀ aryl anhydride)₁₋₁₀₀, (C₉₋₂₀₀₀ alkylaryl anhydride)₁₋₁₀₀, (C₉₋₂₀₀₀ arylalkyl anhydride)₁₋₁₀₀, (C₂₋₃₀ alkyl carbonate)₁₋₁₀₀, (C₇₋₅₀ aryl carbonate)₁₋₁₀₀, (C₈₋₂₀₀₀ alkylaryl carbonate)₁₋₁₀₀, (C₈₋₂₀₀₀ arylalkyl carbonate)₁₋₁₀₀, —R^(a)—O—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₁₋₃₀ alkyl ether, C₆₋₄₀ aryl ether, C₇₋₂₀₀₀ alkylaryl ether, or C₇₋₂₀₀₀ arylalkyl ether)₁₋₁₀₀, —R^(a)—O—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₂₋₅₀ alkyl ester, C₇₋₆₀ aryl ester, C₈₋₂₀₀₀ alkylaryl ester, or C₈₋₂₀₀₀ arylalkyl ester)₁₋₁₀₀, —R^(a)—O—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₁₋₃₀ alkyl ether, C₆₋₄₀ aryl ether, C₇₋₂₀₀₀ alkylaryl ether, or C₇₋₂₀₀₀ arylalkyl ether)₁₋₁₀₀, —CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—, —R^(a)—O—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₂₋₅₀ alkyl ester, C₇₋₆₀ aryl ester, C₈₋₂₀₀₀ alkylaryl ester, or C₈₋₂₀₀₀ arylalkyl ester)₁₋₁₀₀—R^(c)—O—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—, —R^(a)—NH—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₁₋₃₀ alkyl ester, C₆₋₄₀ aryl ether, C₇₋₂₀₀₀ alkylaryl ether, or C₇₋₂₀₀₀ arylalkyl ether)₁₋₁₀₀, —R^(a)—NH—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₂₋₅₀ alkyl ester, C₇₋₆₀ aryl ester, C₈₋₂₀₀₀ alkylaryl ester, or C₈₋₂₀₀₀ arylalkyl ester)₁₋₁₀₀, —R^(a)—NH—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₁₋₃₀ alkyl ether, C₆₋₄₀ aryl ester, C₇₋₂₀₀₀ alkylaryl ether, or C₇₋₂₀₀₀ arylalkyl ether)₁₋₁₀₀—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—, —R^(a)—NH—CO—NH—( R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₂₋₅₀ alkyl ester, C₇₋₆₀ aryl ester, C₈₋₂₀₀₀ alkylaryl ester, or C₈₋₂₀₀₀ arylalkyl ester)₁₋₁₀₀—R^(c)—O—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—, —R^(a)—O—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—NH—(C₂₋₅₀ alkyl amide, C₇₋₆₀ aryl amide, C₈₋₂₀₀₀ alkylaryl amide, or C₈₋₂₀₀₀ arylalkyl amide)₁₋₁₀₀, —R^(a)—NH—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—NH—(C₂₋₅₀ alkyl amide, C₇₋₆₀ aryl amide, C₈₋₂₀₀₀ alkylaryl amide, or C₈₋₂₀₀₀ arylalkyl amide)₁₋₁₀₀, or a bond; each Z, independently, is -G-D, wherein G is —R^(a)—, —R^(a)—Ar—, —Ar—R^(a)—, or —Ar—; and D is —H, —OH, —SH, —NH₂,—NHOH, —SO₃H, —OSO₃H, —CO₂H, —CONH₂, —CONHNH₂, —CH(NH₂)—CO₂H, —NH—CH₂—CO₂H, —P(OH)₃, —PO(OH)₂, —O—PO(OH)₂, —O—PO(OH)—O—PO(OH)₂, —O—PO(O⁻)—O—CH₂CH₂NH₃ ⁺, —O—PO(O⁻)—O—CH₂CH₂—N⁺ (CH₃)₃, -glycoside, -oligosaccharide, —CO-glycoside, —CO-oligosaccharide, —OCH₃, —OCH₂(CHOH)₄—CH₂OH, —OCH₂(CHOH)₂—CH₂OH, —CO—OCH₂(CHOH)₄—CH₂OH, —C₆H₃(OH)₂, —N(CH₂CO₂H)₂, —CO—N(CH₂CO₂H)₂, —CO—NH—C(CH₂CH₂CO₂H)₃, —CO—NH—C(CH₂CH₂OH)₃, —[CH₂—CH(CO₂R^(a))]₁₋₁₀₀—H, —NH₃ ⁺, —N⁺H₂R^(a), —N⁺HR^(a)R^(b), or —N⁺R^(a)R^(b)R^(c), each of R^(a), R^(b), and R^(c), independently, being C₁₋₂₀ alkyl and Ar being aryl; q is 0-30; and m is 0-30; provided that the sum of q and m is 0-30; each of R¹ and R⁴, independently, is ═O or C₁₋₂₀ hydrocarbon; and each of R² and R⁵, independently, is C₁₋₂₀ hydrocarbon; wherein R¹ and R², or R⁴ and R⁵ can join together to form C₆₋₄₀ aryl which is optionally substituted with halide, —OH, —NHNH₂, —NH₂OH, —NH—CH₂—CO₂H, —CH₂—CH₂-D, CH₂—B—Z, —CO—CH₂-D, —CO—B—Z, —O—B—Z, or —NH—B—Z; each of B, D, and Z having been defined above; each of R³ and R⁶, independently, is —H, —CH₂-D, —B—Z, -G-E, -G-CO-E or a side chain of an amino acid; each of B, D, and Z having been defined above, and E being E₁, E₂, or E₃, in which E₁ is Y₁, Y₂-amino, (Y₁, Y₂-alkyl)-amino, Y₁, Y₂-ethylenediamino, (dihydroxymethyl)alkylamino, (X₁, X₃-aryl)amino, or X₁, X₃-aryloxy; E₂ is Y₁, Y₂-alkoxy, (Y₁, Y₂-amino)alkoxy, (Y₁, Y₂, Y₃-aryl)oxy, (dihydroxyalkyl)-aryloxy, (Y₁, Y₂, Y₃-alkyl)amino, (Y₁, Y₂, Y₃-aryl)amino, dihydroxyalkylamino, Y₁, Y₂,Y₃-alkoxy, (trihydroxyalkyl)alkoxy, (trihydroxyalkyl)alkylamino, (dicarboxyalkyl)amino, (Y₁, Y₂, Y₃-alkyl)thio, (X₁, X₃-aryl)thio, (Y₁, Y₂-alkyl)thio, (dihydroxyalkyl)thio, Y₁, Y₂-dioxoalkyl, or tri-(Y₁, Y₂, Y₃-methylaminocarboxyethyl)methylamino; and E₃ is ((glycosidyl)oxoheteroaryl)amino, ((glycosidyl)oxoaryl)amino, (X₁, X₂, X₃-heteroaryl)amino, (X₁-diarylketone)amino, (X, X₁-oxoaryl)amino, (X, X₁-dioxoaryl)amino, (Y₁-alkyl, Y₂-alkyldioxoheteroaryl)amino, (Y₁-alkyl, Y₂-alkyldioxoaryl)amino, (di(Y₁, Y₂-methyl)dioxoheteroaryl)amino, (di(Y₁, Y₂-methyl)dioxoaryl)amino, ((glycosidyl)heteroaryl)amino, ((glycosidyl)aryl)amino, ((carboxylacetylalkyl)oxo-heteroaryl)amino, ((carboxylacetylalkyl)oxoaryl)amino, ((isopropylaminohydroxy-alkoxy)aryl)amino, (X₁, X₂, X₃-alkylaryl)amino, (X₁, X₂, X₃-heteroaryl)oxy, (isopropylaminohydroxyalkyl)aryloxy, (X₁, X₂, X₃-oxoheteroaryl)oxy, (X₁, X₂, X₃-oxoaryl)oxy, (X₁, Y₁-oxoheteroaryl)oxy, (X₁-diarylketone)oxy, (X, X₁-oxoaryl)oxy, (X₁, X₂-dioxoaryl)oxy, (Y₁, Y₂, di-aminodihydroxy)alkyl, (X₁, X₂-heteroaryl)thio, ((tricarboxylalkyl)ethylene-diamino)alkoxy, (X₁, X₂-oxoaryl)thio, (X₁, X₂-dioxoaryl)thio, (glycosidylheteroaryl)thio, (glycosidylaryl)thio, Y₁-alkyl(thiocarbonyl)thio, Y₁, Y₂, -alkyl(thiocarbonyl)thio, Y₁, Y₂, Y₃-alkyl(thiocarbonyl)thio, (Y₁, Y₂-aminothiocarbonyl)thio, (pyranosyl)thio, cysteinyl, tyrosinyl, (phenylalainyl)amino, (dicarboxyalkyl)thio, (aminoaryl)₁₋₁₀₀amino, (pyranosyl)amino, (Y₁-aminoaryl)₁₋₁₀₀amino, (amino(sulfoaryl))₁₋₁₀₀amino, peptidyl, thymidinyl, uridinyl, guanosinyl, adenosinyl, cholesteryl, or biotinylalkoxy; wherein X is halide; each of X₁, X₂, and X₃, independently, is —Y₁, —O—Y₁, —S—Y₁, —NH—Y₁, —CO—O—Y₁, —O—CO—Y₁, —CO—NH—Y₁, —CO—NY₁Y₂, —NH—CO—Y₁, —SO₂—Y₁, —CHY₁Y₂, or —NY₁Y₂; and each of Y₁, Y₂, and Y₃, independently is —Z or —B—Z; each of x and y, independently, is 0 or 1; and s is 1-6; provided that when x is 0, R¹ is ═O; that when y is 0, R⁴ is ═O; that when x is 1, R¹ and R² join together to form C₆₋₄₀ aryl; and that when y is 1, R⁴ and R⁵ join together to form C₆₋₄₀ aryl; and or a salt thereof; the method comprising: reacting a compound of formula (II)

 wherein M is a Cu, Mn, Fe, Co, Ni, Ru, Rh, Os, Zn, Cr, Ti, or Zr ion; with a fullerene compound F_(f) of the formula F(—K)_(m)(—Y—Z)_(q) wherein the sum of q and m is 0 to form a compound of formula (III)

removing M from the compound of formula (III) to form a compound of formula (I) wherein the sum of q and m is 0; and optionally treating the compound of formula (I) wherein the sum of q and m is 0 with a nitrating or sulfating agent to form a nitrofullerene or cyclosulfated fullerene, and contacting the nitrofullerene or cyclosulfated fullerene with a nucleophilic agent to form a compound of formula (I) wherein the sum of q and m is greater than
 0. 25. The method of claim 24, wherein only one of x and y is
 0. 26. The method of claim 25, wherein x is 1, y is 0, and R¹ and R² join together to form a benzene ring.
 27. The method of claim 24, wherein both x and y are
 0. 28. The method of claim 24, wherein M is a Cu ion.
 29. The method of claim 24, wherein the compound of formula (II) is prepared by reacting a compound of formula (IV)

with a metal salt MX, wherein M has been defined above, and X is an anion.
 30. The method of claim 29, wherein X is halide, sulfate, nitrate, or acetate.
 31. The method of claim 29, wherein the compound of formula (IV) is prepared by reacting a compound of formula (V)

with a compound of formula (VI)


32. The method of claim 31, wherein each of R³ and R⁶, independently, is —H, —B—Z, -G-E, -G-CO-E, or a side chain of an amino acid, wherein B, E, G, and Z have been defined above.
 33. A compound of formula (VII):

wherein F_(f) is F(—K)_(m)(—Y—Z)_(q) in which F is a fullerene core; each K, independently, is —OH, —SH, —NH₂, —NHOH, —SO₃H, —OSO₃H, —CO₂H, —CONH₂, —CONHNH₂, —P(OH)₃, —PO(OH)₂,—O—PO(OH)₂,—O—PO(OH)—O—PO(OH)₂, —O—PO(O⁻)—O—CH₂CH₂—NH₃ ⁺, —O—PO(O⁻)—O—CH₂CH₂—N⁺ (CH₃)₃, -glycoside, —OCH₃, —OCH₂(CHOH)₄—CH₂OH, —OCH₂(CHOH)₂—CH₂OH, —NH—CH₂—CO₂H, —[CH(CO₂H)—CH₂]₁₋₁₀₀—OH, —[CH(CO₂R^(a))—CH₂]₁₋₁₀₀—OH, —[C(CH₃)(CO₂H)—CH₂]₁₋₁₀₀—OH, —[C(CH₃)(CO₂R^(a))—CH₂]₋₁₀₀—OH, —N(OH)₂, —NH₃ ⁺, —N⁺H₂R^(a), —N⁺HR^(a)R^(b), or —N⁺R^(a)R^(b)R^(c); each Y is -A-B—, in which A is —O—, —NH—, —S—, —CO—O—, —O—CO—, —O—CO—O—, —O—CO—NH—, —NH—CO—NH—, —CO—NH—, or —NH—CO—; and B is —R^(a)—O—[Si(CH₃)₂—O—]₁₋₁₀₀, C₁₋₂₀₀₀ alkyl, C₆₋₄₀ aryl, C₇₋₂₀₀₀ alkylaryl, C₇₋₂₀₀₀ arylalkyl, (C₁₋₃₀ alkyl ether)₁₋₁₀₀, (C₆₋₄₀ aryl ether)₁₋₁₀₀, (C₇₋₂₀₀₀ alkylaryl ether) ₁₋₁₀₀, (C₇₋₂₀₀₀ arylalkyl ether)₁₋₁₀₀, (C₁₋₃₀ alkyl thioether)₁₋₁₀₀, (C₆₋₄₀ aryl thioether)₁₋₁₀₀, C₇₋₂₀₀₀ alkylaryl thioether)₁₋₁₀₀, (C₇₋₂₀₀₀ arylalkyl thioether)₁₋₁₀₀, (C₂₋₅₀ alkyl ester)₁₋₁₀₀, (C₇₋₂₀₀₀ aryl ester)₁₋₁₀₀, (C₈₋₂₀₀₀ alkylaryl ester)₁₋₁₀₀, (C₈₋₂₀₀₀ arylalkyl ester)₁₋₁₀₀, —R^(a)—CO—O—(C₁₋₃₀ alkyl ether)₁₋₁₀₀, —R^(a)—CO—O—(C₆₋₄₀ aryl ether)₁₋₁₀₀, —R^(a)—CO—O—(C₇₋₂₀₀₀ alkylaryl ether)₁₋₁₀₀, —R^(a)—CO—O—(C₇₋₂₀₀₀ arylalkyl ether)₁₋₁₀₀, (C₄₋₅₀ alkyl urethane)₁₋₁₀₀, (C₁₄₋₆₀ aryl urethane)₁₋₁₀₀, (C₁₀₋₂₀₀₀ alkylaryl urethane)₁₋₁₀₀, (C₁₀₋₂₀₀₀ arylalkyl urethane)₁₋₁₀₀, (C₅₋₅₀ alkyl urea)₁₋₁₀₀, (C₁₄₋₆₀ aryl urea)₁₋₁₀₀, (C₁₀₋₂₀₀₀ alkylaryl urea)₁₋₁₀₀, (C₁₀₋₂₀₀₀ arylalkyl urea)₁₋₁₀₀, (C₂₋₅₀ alkyl amide)₁₋₁₀₀, (C₇₋₆₀ aryl amide)₁₋₁₀₀, (C₈₋₂₀₀₀ alkylaryl amide)₁₋₁₀₀, (C₈₋₂₀₀₀ arylalkyl amide)₁₋₁₀₀, (C₃₋₃₀ alkyl anhydride)₁₋₁₀₀, (C₈₋₅₀ aryl anhydride)₁₋₁₀₀, (C₉₋₂₀₀₀ alkylaryl anhydride)₁₋₁₀₀, (C₉₋₂₀₀₀ arylalkyl anhydride)₁₋₁₀₀, (C₂₋₃₀ alkyl carbonate)₁₋₁₀₀, (C₇₋₅₀ aryl carbonate)₁₋₁₀₀, (C₈₋₂₀₀₀ alkylaryl carbonate)₁₋₁₀₀, (C₈₋₂₀₀₀ arylalkyl carbonate)₁₋₁₀₀, —R^(a)—O—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₁₋₃₀ alkyl ether, C₆₋₄₀ aryl ether, C₇₋₂₀₀₀ alkylaryl ether, or C₇₋₂₀₀₀ arylalkyl ether)₁₋₁₀₀)—R^(a)—O—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₂₋₅₀ alkyl ester, C₇₋₆₀ aryl ester, C₈₋₂₀₀₀ alkylaryl ester, or C₈₋₂₀₀₀ arylalkyl ester)₁₋₁₀₀, —R^(a)—O—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₁₋₃₀ alkyl ether, C₆₋₄₀ aryl ether, C₇₋₂₀₀₀ alkylaryl ether, or C₇₋₂₀₀₀ arylalkyl ether)₁₋₁₀₀—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—, —R^(a)—O—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₂₋₅₀ alkyl ester, C₇₋₆₀ aryl ester, C₈₋₂₀₀₀ alkylaryl ester, or C₈₋₂₀₀₀ arylalkyl ester)₁₋₁₀₀—R^(c)—O—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—, —R^(a)—NH—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₁₋₃₀ alkyl ether, C₆₋₄₀ aryl ether, C₇₋₂₀₀₀ alkylaryl ether, or C₇₋₂₀₀₀ arylalkyl ether)₁₋₁₀₀, —R^(a)—NH—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₂₋₅₀ alkyl ester, C₇₋₆₀ aryl ester, C₈₋₂₀₀₀ alkylaryl ester, or C₈₋₂₀₀₀ arylalkyl ester)₁₋₁₀₀, —R^(a)—NH—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₁₋₃₀ alkyl ether, C₆₋₄₀ aryl ether, C₇₋₂₀₀₀ alkylaryl ether, or C₇₋₂₀₀₀ arylalkyl ether)₁₋₁₀₀—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—, —R^(a)—NH—CO—NH—(R^(b) or Ar—R^(b)Ar)—NH—CO—O—(C₂₋₅₀ alkyl ester, C₇₋₆₀ aryl ester, C₈₋₂₀₀₀ alkylaryl ester, or C₈₋₂₀₀₀ arylalkyl ester)₁₋₁₀₀—R^(c)—O—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—, —R^(a)—O—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—NH—(C₂₋₅₀ alkyl amide, C₇₋₆₀ aryl amide, C₈₋₂₀₀₀ alkylaryl amide, or C₈₋₂₀₀₀ arylalkyl amide)₁₋₁₀₀, —R^(a)—NH—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—NH—(C₂₋₅₀ alkyl amide, C₇₋₆₀ aryl amide, C₈₋₂₀₀₀ alkylaryl amide, or C₈₋₂₀₀₀ arylalkyl amide)₁₋₁₀₀, or a bond; each Z, independently, is -G-D, wherein G is —R^(a)—, —R^(a)—Ar—, —Ar—R^(a)—, or —Ar—; and D is —H, —OH, —SH, —NH₂, —NHOH, —SO₃H, —OSO₃H, —CO₂H, —CONH₂, —CONHNH₂, —CH(NH₂)—CO₂H, —NH—CH₂—CO₂H, —P(OH)₃, —PO(OH)₂, —O—PO(OH)₂, —O—PO(OH)—O—PO(OH)₂,—O—PO(O⁻)—O—CH₂CH₂NH₃ ⁺, —O—PO(O⁻)—O—CH₂CH₂—N⁺ (CH₃)₃, -glycoside, -oligosaccharide, —CO-glycoside, —CO-oligosaccharide, —OCH₃, —OCH₂(CHOH)₄—CH₂OH, —OCH₂(CHOH)₂—CH₂OH, —CO—OCH₂(CHOH)₄—CH₂OH, —C₆H₃(OH)₂, —N(CH₂—CO₂H)₂, —CO—N(CH₂CO₂H)₂, —CO—NH—C(CH₂CH₂CO₂H)₃, —CO—NH—C(CH₂CH₂OH)₃, —[CH₂—CH(CO₂R^(a))]₁₋₁₀₀—H, —NH₃ ⁺, —N⁺H₂R^(a), —N⁺HR^(a)R^(b), or —N⁺R^(a)R^(b)R^(c), each of R^(a), R^(b), and R^(c), independently, being C₁₋₂₀ alkyl and Ar being aryl; q is 0-30; and m is 0-30; provided that the sum of q and m is 0-30; each of R¹ and R⁴, independently, is ═O or C₁₋₂₀ hydrocarbon; and each of R² and R⁵, independently, is C₁₋₂₀ hydrocarbon; wherein R¹ and R², or R⁴ and R⁵ can join together to form C₆₋₄₀ aryl which is optionally substituted with halide, —OH, —NHNH₂, —NH₂OH, —NH—CH₂—CO₂H, —CH₂—CH₂-D, CH₂—B—Z, —CO—CH₂-D, —CO—B—Z, —O—B—Z, or —NH—B—Z; each of B, D, and Z having been defined above; each of R³ and R⁶, independently, is —H, —CH₂-D, —B—Z, -G-E, -G-CO-E or a side chain of an amino acid; each of B, D, and Z having been defined above, and E being E₁, E₂, or E₃, in which E₁ is Y₁, Y₂-amino, (Y₁, Y₂-alkyl)-amino, Y₁, Y₂-ethylenediamino, (dihydroxymethyl)alkylamino, (X₁, X₃-aryl)amino, or X₁, X₃-aryloxy; E₂ is Y₁, Y₂-alkoxy, (Y₁, Y₂-amino)alkoxy, (Y₁, Y₂, Y₃-aryl)oxy, (dihydroxyalkyl)-aryloxy, (Y₁, Y₂, Y₃-alkyl)amino, (Y₁, Y₂, Y₃-aryl)amino, dihydroxyalkylamino, Y₁, Y₂, Y₃-alkoxy, (trihydroxyalkyl)alkoxy, (trihydroxyalkyl)alkylamino, (dicarboxyalkyl)amino, (Y₁, Y₂, Y₃-alkyl)thio, (X₁, X₃-aryl)thio, (Y₁, Y₂-alkyl)thio, (dihydroxyalkyl)thio, Y₁, Y₂-dioxoalkyl, or tri-(Y₁, Y₂, Y₃-methylaminocarboxyethyl)methylamino; and E₃ is ((glycosidyl)oxoheteroaryl)amino, ((glycosidyl)oxoaryl)amino, (X₁, X₂, X₃-heteroaryl)amino, (X₁-diarylketone)amino, (X, X₁-oxoaryl)amino, (X, X₁-dioxoaryl)amino, (Y₁-alkyl, Y₂-alkyldioxoheteroaryl)amino, (Y₁-alkyl, Y₂-alkyldioxoaryl)amino, (di(Y₁, Y₂-methyl)dioxoheteroaryl)amino, (di(Y₁, Y₂-methyl)dioxoaryl)amino, ((glycosidyl)heteroaryl)amino, ((glycosidyl)aryl)amino, ((carboxylacetylalkyl)oxo-heteroaryl)amino, ((carboxylacetylalkyl)oxoaryl)amino, ((isopropylaminohydroxy-alkoxy)aryl)amino, (X₁, X₂, X₃-alkylaryl)amino, (X₁, X₂, X₃-heteroaryl)oxy, (isopropylaminohydroxyalkyl)aryloxy, (X₁, X₂, X₃-oxoheteroaryl)oxy, (X₁, X₂, X₃-oxoaryl)oxy, (X₁, Y₁-oxoheteroaryl)oxy, (X₁-diarylketone)oxy, (X, X₁-oxoaryl)oxy, (X₁, X₂-dioxoaryl)oxy, (Y₁, Y₂, di-aminodihydroxy)alkyl, (X₁, X₂-heteroaryl)thio, ((tricarboxylalkyl)ethylene-diamino)alkoxy, (X₁, X₂-oxoaryl)thio, (X₁, X₂-dioxoaryl)thio, (glycosidylheteroaryl)thio, (glycosidylaryl)thio, Y₁-alkyl(thiocarbonyl)thio, Y₁, Y₂, -alkyl(thiocarbonyl)thio, Y₁, Y₂, Y₃-alkyl(thiocarbonyl)thio, (Y₁, Y₂-aminothiocarbonyl)thio, (pyranosyl)thio, cysteinyl, tyrosinyl, (phenylalainyl)amino, (dicarboxyalkyl)thio, (aminoaryl)₁₋₁₀₀amino, (pyranosyl)amino, (Y₁-aminoaryl)₁₋₁₀₀amino, (amino(sulfoaryl))₁₋₁₀₀amino, peptidyl, thymidinyl, uridinyl, guanosinyl, adenosinyl, cholesteryl, or biotinylalkoxy; wherein X is halide; each of X₁, X₂, and X₃, independently, is —Y₁, —O—Y₁, —S—Y₁, —NH—Y₁, —CO—O—Y₁, —O—CO—Y₁, —CO—NH—Y₁, —CO—NY₁Y₂, —NH—CO—Y₁, —SO₂—Y₁, —CHY₁Y₂, or —NY₁Y₂; and each of Y₁, Y₂, and Y₃, independently, is —Z or —B—Z; B and Z having been defined above; R⁷ is —R^(d) or —O—R^(e); wherein R^(d) is —OH, —OM, —NHNH₂, —NHOH, —NH—CH₂—CO₂H, —O—B—Z, —NH—B—Z, -E, —O-G-E, —NH-G-E, —O-G-CO-E, or —NH-G-CO-E; M being Cu, Mn, Fe, Co, Ni, Ru, Rh, Os, Zn, Cr, Ti, or Zr ion; and R^(e) is —H, —CH₂—CH₂-D, —CH₂—B—Z, —CH₂-G-E, -—H₂-G-CO-E, —CO—CH₂-D, —CO—B—Z, —CO-G-E, or —CO-G-CO-E; each of B, D, E, G, and Z having been defined above; R⁸ is R^(e); R⁹ is —O— or a bond; R¹⁰ is —R^(d) or —R^(e); each of which having been defined above; each of x and y, independently, is 0 or 1; and p is 1-30; provided that when x is 0, R¹ is ═O, and R⁷ is —R^(d); that when y is 0, R⁴ is ═O, and R⁹ is a bond, and R¹⁰ is —R^(d); that when x is 1, R¹ and R² join together to form C₆₋₄₀ aryl, and R⁷ is —O—R^(e); and that when y is 1, R⁴ and R⁵ join together to form C₆₋₄₀ aryl, R⁹ is —O—, and R¹⁰ is —R^(e); and further provided that when p is greater than 1, x is 0; or a salt thereof.
 34. The compound of claim 33, wherein F is C₆₀, C₆₁, C₆₂, C₆₃, C₆₄, C₆₅, C₇₀, C₇₆, C₇₈, C₈₂, C₈₄, or C₉₂, or La@C_(n), Ho@C_(n), Gd@C_(n), or Er@C_(n), in which n is 60, 74, or
 82. 35. The compound of claim 33, wherein the sum of q and m is 0-20.
 36. The compound of claim 33, wherein p is 2-10.
 37. The compound of claim 33, wherein each of R³ and R⁶, independently, is —H, —B—Z, -G-E, G-CO-E or a side chain of an amino acid.
 38. The compound of claim 33, wherein R^(d) is —OH, —NHNH₂, -E, -O-G-E, —NH-G-E, —O-G-CO-E, or —NH-G-CO-E.
 39. The compound of claim 33, wherein R^(e) is —H, —CH₂-G-E, —CH₂-G-CO-E, —CO-G-E, or —CO-G-CO-E.
 40. The compound of claim 33, wherein both x and y are
 0. 41. The compound of claim 40, wherein R^(d) is —OH, —NHNH₂, -E, —O-G-E, —NH-G-E, —O-G-CO-E, or —NH-G-CO-E.
 42. The compound of claim 41, wherein R^(e) is —H, —CH₂-G-E, —CH₂-G-CO-E, —CO-G-E, or —CO-G-CO-E.
 43. The compound of claim 42, wherein p is 2-10.
 44. The compound of claim 43, said compound is oligo(1,3-dimethyl-fulleropyrrolidine-1,3-dicarboxylic N-amide).
 45. A compound of formula (VIII):

wherein F_(f) is F(—K)_(m)(—Y—Z)_(q) in which F is a fullerene core; each K, independently, is —OH, —SH, —NH₂, —NHOH, —SO₃H, —OSO₃H, —CO₂H, —CONH₂, —CONHNH₂, —P(OH)₃, —PO(OH)₂, —O—PO(OH)₂, —O—PO(OH)—O—PO(O⁻)₂, —O—PO(OH)—O—CH₂CH₂—NH₃ ⁺, —O—PO(O⁻)—O—CH₂CH₂—N⁺ (CH₃)₃, -glycoside, —OCH₃, —OCH₂(CHOH)₄—CH₂OH, OCH₂(CHOH)₂—CH₂OH, —NH—CH₂—CO₂H, —[CH(CO₂H)—CH₂]₁₋₁₀₀—OH, —[CH(CO₂R^(a))—CH₂]₁₋₁₀₀—OH, —[C(CH₃)(CO₂H)—CH₂]₁₋₁₀₀—OH, —[C(CH₃)(CO₂R^(a))—CH₂]₁₋₁₀₀—OH, —N(OH)₂, —NH₃ ⁺, —N⁺H₂R^(a), —N⁺HR^(a)R^(b), or —N⁺R^(a)R^(b)R^(c); each Y is -A-B—, in which A is —O—, —NH—, —S—, —CO—O—, —O—CO—, —O—CO—O—, —O—CO—NH—, —NH—CO—NH—, —CO—NH—, or —NH—CO—; and B is —R^(a)—O—[Si(CH₃)₂—O—]₁₋₁₀₀, C₁₋₂₀₀₀ alkyl, C₆₋₄₀ aryl, C₇₋₂₀₀₀ alkylaryl, C₇₋₂₀₀₀ arylalkyl, (C₁₋₃₀ alkyl ether)₁₋₁₀₀, (C₆₋₄₀ aryl ether)₁₋₁₀₀, (C₇₋₂₀₀₀ alkylaryl ether)₁₋₁₀₀, (C₇₋₂₀₀₀ arylalkyl ether)₁₋₁₀₀, (C₁₋₃₀ alkyl thioether)₁₋₁₀₀, (C₆₋₄₀ aryl thioether)₁₋₁₀₀, (C₇₋₂₀₀₀ alkylaryl thioether)₁₋₁₀₀, (C₇₋₂₀₀₀ arylalkyl thioether)₁₋₁₀₀, (C₂₋₅₀ alkyl ester)₁₋₁₀₀, (C₇₋₂₀₀₀ aryl ester)₁₋₁₀₀, (C₈₋₂₀₀₀ alkylaryl ester)₁₋₁₀₀, (C₈₋₂₀₀₀ arylalkyl ester)₁₋₁₀₀, —R^(a)—CO—O—(C₁₋₃₀ alkyl ether)₁₋₁₀₀, —R^(a)—CO—O—(C₆₋₄₀ aryl ether)₁₋₁₀₀, —R^(a)—CO—O—(C₇₋₂₀₀₀ alkylaryl ether)₁₋₁₀₀, —R^(a)—CO—O—(C₇₋₂₀₀₀ arylalkyl ether)₁₋₁₀₀, (C₄₋₅₀ alkyl urethane)₁₋₁₀₀, (C₁₄₋₆₀ aryl urethane)₁₋₁₀₀, (C₁₀₋₂₀₀₀ alkylaryl urethane)₁₋₁₀₀, (C₁₀₋₂₀₀₀ arylalkyl urethane)₁₋₁₀₀, (C₅₋₅₀ alkyl urea)₁₋₁₀₀, (C₁₄₋₆₀ aryl urea)₁₋₁₀₀, (C₁₀₋₂₀₀₀ alkylaryl urea)₁₋₁₀₀, (C₁₀₋₂₀₀₀ arylalkyl urea)₁₋₁₀₀, (C₂₋₅₀ alkyl amide)₁₋₁₀₀, (C₇₋₆₀ aryl amide)₁₋₁₀₀, (C₈₋₂₀₀₀ alkylaryl amide)₁₋₁₀₀, (C₈₋₂₀₀₀ arylalkyl amide)₁₋₁₀₀, (C₃₋₃₀ alkyl anhydride)₁₋₁₀₀, (C₈₋₅₀ aryl anhydride)₁₋₁₀₀, (C₉₋₂₀₀₀ alkylaryl anhydride)₁₋₁₀₀, (C₉₋₂₀₀₀ arylalkyl anhydride)₁₋₁₀₀, (C₂₋₃₀ alkyl carbonate)₁₋₁₀₀, (C₇₋₅₀ aryl carbonate)₁₋₁₀₀, (C₈₋₂₀₀₀ alkylaryl carbonate)₁₋₁₀₀, (C₈₋₂₀₀₀ arylalkyl carbonate)₁₋₁₀₀, —R^(a)—O—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₁₋₃₀ alkyl ether, C₆₋₄₀ aryl ether, C₇₋₂₀₀₀ alkylaryl ether, or C₇₋₂₀₀₀ arylalkyl ether)₁₋₁₀₀, —R^(a)—O—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₂₋₅₀ alkyl ester, C₇₋₆₀ aryl ester, C₈₋₂₀₀₀ alkylaryl ester, or C₈₋₂₀₀₀ arylalkyl ester)₁₋₁₀₀, —R^(a)—O—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₁₋₃₀ alkyl ether, C₆₋₄₀ aryl ether, C₇₋₂₀₀₀ alkylaryl ether, or C₇₋₂₀₀₀ arylalkyl ether)₁₋₁₀₀, —CO—NH—(R^(b) or Ar —R^(b)—Ar)—NH—CO—O—, —R^(a)—O—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₂₋₅₀ alkyl ester, C₇₋₆₀ aryl ester, C₈₋₂₀₀₀ alkylaryl ester, or C₈₋₂₀₀₀ arylalkyl ester)₁₋₁₀₀—R^(c)—O—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—, —R^(a)—NH—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₁₋₃₀ alkyl ether, C₆₋₄₀ aryl ether, C₇₋₂₀₀₀ alkylaryl ether, or C₇₋₂₀₀₀ arylalkyl ether)₁₋₁₀₀, —R^(a)—NH—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₂₋₅₀ alkyl ester, C₇₋₆₀ aryl ester, C₈₋₂₀₀₀ alkylaryl ester, or C₈₋₂₀₀₀ arylalkyl ester)₁₋₁₀₀, —R^(a)—NH—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₁₋₃₀ alkyl ether, C₆₋₄₀ aryl ether, C₇₋₂₀₀₀ alkylaryl ether, or C₇₋₂₀₀₀ arylalkyl ether)₁₋₁₀₀—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—, —R^(a)—NH—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—(C₂₋₅₀ alkyl ester, C₇₋₆₀ aryl ester, C₈₋₂₀₀₀ alkylaryl ester, or C₈₋₂₀₀₀ arylalkyl ester)l₁₋₁₀₀—R^(c)—O—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—O—, —R^(a)—O—CO—NH—(R^(b) or Ar—R_(b)—Ar)—NH—CO—NH—(C₂₋₅₀ alkyl amide, C₇₋₆₀ aryl amide, C₈₋₂₀₀₀ alkylaryl amide, or C₈₋₂₀₀₀ arylalkyl amide)₁₋₁₀₀, —R^(a)—NH—CO—NH—(R^(b) or Ar—R^(b)—Ar)—NH—CO—NH—(C₂₋₅₀ alkyl amide, C₇₋₆₀ aryl amide, C₈₋₂₀₀₀ alkylaryl amide, or C₈₋₂₀₀₀ arylalkyl amide)₁₋₁₀₀,or a bond; each Z, independently, is -G-D, wherein G is —R^(a)—, —R^(a)—Ar—, —Ar—R^(a)—, or —Ar—; and D is —H, —OH, —SH, —NH₂, —NHOH, —SO₃H, —OSO₃H, —CO₂H, —CONH₂, —CONHNH₂, —CH(NH₂)—CO₂H, —NH—CH₂—CO₂H, —P(OH)₃, —PO(OH)₂, —O—PO(OH)₂, —O—PO(OH)—O—PO(OH)₂, —O—PO(O⁻)—O—CH₂CH₂NH₃ ⁺, —O—PO(O⁻)—O—CH₂CH₂—N⁺ (CH₃)₃, -glycoside, -oligosaccharide, —CO-glycoside, —CO-oligosaccharide, —OCH₃, —OCH₂(CHOH)₄—CH₂OH, —OCH₂(CHOH)₂—CH₂OH, —CO—OCH₂(CHOH)₄—CH₂OH, —C₆H₃(OH)₂, —N(CH₂CO₂H)₂, —CO—N(CH₂CO₂H)₂, —CO—NH—C(CH₂CH₂CO₂H)₃, —CO—NH—C(CH₂CH₂OH)₃, —[CH₂—CH(CO₂R^(a))]₁₋₁₀₀—H, —NH₃ ⁺, —N⁺H₂R^(a), —N⁺HR^(a)R^(b), or —N⁺R^(a)R^(b)R^(c), each of R^(a), R^(b), and R^(c), independently, being C₁₋₂₀ alkyl and Ar being aryl; q is 0-30; and m is 0-30; provided that the sum of q and m is 0-30; each of R¹ and R⁴, independently, is ═O or C₁₋₂₀ hydrocarbon; and each of R² and R⁵, independently, is C₁₋₂₀ hydrocarbon; wherein R¹ and R², or R⁴ and R⁵ can join together to form C₆₋₄₀ aryl which is optionally substituted with halide, —OH, —NHNH₂, —NH₂OH, —NH—CH₂—CO₂H, —CH₂—CH₂-D, —CH₂—B—Z, —CO—CH₂-D, -CO—B—Z, —O—B—Z, or —NH—B—Z; each of B, D, and Z having been defined above; each of R³ and R⁶, independently, is —H, —CH₂-D, —B—Z, -G-E, G-CO-E or a side chain of an amino acid; each of B, D, and Z having been defined above, and E being E₁, E₂, or E₃, in which E₁ is Y₁, Y₂-amino, (Y₁, Y₂-alkyl)-amino, Y₁, Y₂-ethylenediamino, (dihydroxymethyl)alkylamino, (X₁, X₃-aryl)amino, or X₁, X₃-aryloxy; E₂ is Y₁, Y₂-alkoxy, (Y₁, Y₂-amino)alkoxy, (Y₁, Y₂, Y₃-aryl)oxy, (dihydroxyalkyl)-aryloxy, (Y₁, Y₂, Y₃-alkyl)amino, (Y₁, Y₂, Y₃-aryl)amino, dihydroxyalkylamino, Y₁, Y₂, Y₃-alkoxy, (trihydroxyalkyl)alkoxy, (trihydroxyalkyl)alkylamino, (dicarboxyalkyl)amino, (Y₁, Y₂, Y₃-alkyl)thio, (X₁, X₃-aryl)thio, (Y₁, Y₂-alkyl)thio, (dihydroxyalkyl)thio, Y₁, Y₂-dioxoalkyl, or tri-(Y₁, Y₂, Y₃-methylaminocarboxyethyl)methylamino; and E₃ is ((glycosidyl)oxoheteroaryl)amino, ((glycosidyl)oxoaryl)amino, (X₁, X₂, X₃-heteroaryl)amino, (X₁-diarylketone)amino, (X₁, X₁-oxoaryl)amino, (X₁, X₁-dioxoaryl)amino, (Y₁-alkyl, Y₂-alkyldioxoheteroaryl)amino, (Y₁-alkyl, Y₂-alkyldioxoaryl)amino, (di(Y₁, Y₂-methyl)dioxoheteroaryl) amino, (di(Y₁, Y₂-methyl)dioxoaryl)amino, ((glycosidyl)heteroaryl)amino, ((glycosidyl)aryl)amino, ((carboxylacetylalkyl)oxo-heteroaryl)amino, ((carboxylacetylalkyl)oxoaryl)amino, ((isopropylaminohydroxy-alkoxy)aryl)amino, (X₁, X₂, X₃-alkylaryl)amino, (X₁, X₂, X₃-heteroaryl)oxy, (isopropylaminohydroxyalkyl)aryloxy, (X₁, X₂, X₃-oxoheteroaryl)oxy, (X₁, X₂, X₃-oxoaryl)oxy, (X₁, Y₁-oxoheteroaryl)oxy, (X₁-diarylketone)oxy, (X₁, X₁-oxoaryl)oxy, (X₁, X₂-dioxoaryl)oxy, (Y₁, Y₂, di-aminodihydroxy)alkyl, (X₁, X₂-heteroaryl)thio, ((tricarboxylalkyl)ethylene-diamino)alkoxy, (X₁, X₂-oxoaryl)thio, (X₁, X₂-dioxoaryl)thio, (glycosidylheteroaryl)thio, (glycosidylaryl)thio, Y₁-alkyl(thiocarbonyl)thio, Y₁ , Y₂, -alkyl(thiocarbonyl)thio, Y₁, Y₂, Y₃-alkyl(thiocarbonyl)thio, (Y₁, Y₂-aminothiocarbonyl)thio, (pyranosyl)thio, cysteinyl, tyrosinyl, (phenylalainyl)amino, (dicarboxyalkyl)thio, (aminoaryl)₁₋₁₀₀amino, (pyranosyl)amino, (Y₁-aminoaryl)₁₋₁₀₀amino, (amino(sulfoaryl))₁₋₁₀₀amino, peptidyl, thymidinyl, uridinyl, guanosinyl, adenosinyl, cholesteryl, or biotinylalkoxy; wherein X is halide; each of X₁, X₂, and X₃, independently, is —Y₁, —O—Y₁, —S—Y₁, —NH—Y₁, —CO—O—Y₁, —O—CO—Y₁, —CO—NH—Y₁, —CO—NY₁, Y₂, —NH—CO—Y₁, —SO₂—Y₁, —CHY₁Y₂, or —NY₁Y₂; and each of Y₁, Y₂, and Y₃, independently, is —Z or —B—Z; B and Z having been defined above; R⁷ is —R^(d) or —O—R^(e); wherein R^(d) is —OH, —OM, —NHNH₂, —NHOH, —NH—CH₂—CO₂H, —O—B—Z, —NH—B—Z, -E, —O-G-E, —NH-G-E, —O-G-CO-E, or —NH-G-CO-E; M being Cu, Mn, Fe, Co, Ni, Ru, Rh, Os, Zn, Cr, Ti, or Zr ion; and R^(e) is —H, —CH₂—CH₂-D, —CH₂—B—Z, —CH₂-G-E, —CH₂-G-CO-E, —CO—CH₂-D, —CO—B—Z, —CO-G-E, or —CO-G-CO-E; each of B, D, E, G, and Z having been defined above; R⁸ is R^(e), which has the same meaning as set forth above; R⁹ is —O—R^(f)— or —R^(g)—; wherein R^(f) is —CO—B-G-O—, —CO—B-G-NH—, —CO—-B-G-CO—O—, or —CO—B-G-CO—NH—; and R^(g) is —NH—, —O—, —O—B-G-O—, —NH—B-G-O—, —NH—B-G-NH—, —O—CO—B-G-CO—O—, or —NH—CO—B-G-CO—NH—; B and G having been defined above; R¹⁰ is —H; each of x and y, independently, is 0 or 1; and r is 1-100; provided that when x is 0, R¹ is ═O, and R⁷ is —R^(d); that when y is 0, R⁴ is ═O, and R⁹ is —R^(g), and R¹⁰ is —H; that when x is 1, R¹ and R² join together to form C₆₋₄₀ aryl, and R⁷ is —O—R^(e); and that when y is 1, R⁴ and R⁵ join together to form C₆ ₆₋₄₀ aryl, R⁹ is —O—R^(f), and R¹⁰ is —H; and further provided that when r is greater than 1, x is 0; or a salt thereof.
 46. The compound of claim 45, wherein F is C₆₀, C₆₁, C₆₂, C₆₃, C₆₄, C₆₅, C₇₀, C₇₆, C₇₈, C₈₂, C₈₄, or C₉₂, or La@C_(n), Ho@C_(n), Gd@C_(n), or Er@C_(n), in which n is 60, 74, or
 82. 47. The compound of claim 45, wherein the sum of q and m is 0-20.
 48. The compound of claim 45, wherein r is 2-30.
 49. The compound of claim 45, wherein each of R³ and R⁶, independently, is —H, —B—Z, -G-E, -G-CO-E, or a side chain of an amino acid.
 50. The compound of claim 45, wherein R^(d) is —OH, —NHNH₂, -E, —O-G-E, —NH-G-E, —O-G-CO-E, or —NH-G-CO-E.
 51. The compound of claim 45, wherein R^(e) is —H, —CH₂-G-E, —CH₂-G-CO-E, 13 CO-G-E, or —CO-G-CO-E.
 52. The compound of claim 45, wherein R^(f) is —CO-B-G-NH— or —CO-B-G-CO—NH—.
 53. The compound of claim 45, wherein R^(g) is —O—B-G-O—, —NH—B-O—, —NH—B-G-NH—, —O—CO—B-G-CO—O—, or —NH—CO—B-G-CO—NH—.
 54. The compound of claim 45, wherein both x and y are
 0. 55. The compound of claim 54, wherein each of R³ and R⁶, independently, is —H, —B—Z, -G-E, -G-CO-E, or a side chain of an amino acid.
 56. The compound of claim 55, wherein R^(d) is —OH, —NHNH₂, -E, —O-G-E, —NH-G-E, —O-G-CO-E, or —NH-G-CO-E.
 57. The compound of claim 56, wherein R^(e) is —H, —CH₂-G-E, —CH₂-G-CO-E, —CO-G-E, or —CO-G-CO-E.
 58. The compound of claim 57, wherein R^(f) is —CO—B-G-NH— or —CO—B-G-CO—NH—.
 59. The compound of claim 58, wherein R^(g) is —O-B-G-O—, —NH—B-G-O—, —NH—B—G-NH—, —O—CO—B-G-CO—O—, or —NH—CO—B-G-CO—NH—.
 60. The compound of claim 59, wherein r is 2-30. 